Condensed heterocyclic compound

FIELD: chemistry.

SUBSTANCE: invention relates to new condensed compounds (versions) or their pharmaceutically acceptable salts having inhibitory effect on HER2 and/or EGFR kinase, having the following formula, for example: or , where R1a is a hydrogen atom; R2a is a C1-8alkyl group, C2-8alkenyl group or C2-8alkynyl group, each of which is substituted with substitute(s), R3a is a hydrogen atom or C1-6alkyl group; or R1a and R2a are optionally bonded with formation or R2a and R3a are optionally bonded with formation of C2-4alkylene; Ba is a benzene ring optionally substituted with 1-4 substitutes selected from halogen and optionally halogenated C1-4alkyl; Ca is a phenyl group substituted with 1-5 substitutes selected from (i) halogen, (ii) optionally halogenated C1-4alkyl, (iii) hydroxy- C1-4alkyl, (iv) a 5-8-member heterocycle- C1-4alkyl, where the said 5-8-member heterocycle contains 1-3 heteroatoms selected from a nitrogen atom, oxygen atom and optionally oxidised sulphur atom, (v) optionally halogenated C1-4alkyloxy, (vi) cyano and (vii) carbamoyl, optionally substituted with C1-8alkyl, and, respectively, R2e is a C1-4alkyl group optionally substituted with -O-(CH2)n-OH, where n is an integer from 1 to 4; R3e is a hydrogen atom; Be is a benzene ring optionally substituted with a halogen; and Ce is a phenyl group optionally substituted with halogenated C1-4alkyl.

EFFECT: obtained new compounds can be used for treating cancer.

22 cl, 2 tbl, 280 ex

 

The technical field to which the invention relates.

The present invention relates to a condensed pyrimidine derivative having inhibitory activity against tyrosinekinase of growth factor receptor, which is useful for the prevention or treatment of cancer, the method of its production and to its use.

Background of invention

Gene cell growth factor and growth factor receptor called protooncogenes, and it plays a key role in the pathology of tumors in humans. Family (erbB) receptors growth factor epithelial cells includes EGFR, HER2, her3, and HER4, which are receptor tyrosine kinases type I. Specified erbB family is expressed in different groups of cells and deeply involved in the regulation of growth and differentiation of cells and the regulation of suppression of cell death (suppression of apoptosis). Empirically it is known that, for example, high expression of EGFR and HER2 and homeostatic activation of receptors transform cells.

It is also known that high expression and simultaneous expression of each of these receptors are adverse prognostic factors in patients with various forms of cancer.

These receptors are associated with many peptide ligands, such as EGF, TGFα, and the like, and the binding of the ligand promotes Homo - and who and heterodimerization receptors. This induces the increase of kinase activity as a result of samopozhervovanija or transphosphorylation receptors and causes activation below in the course of the reactions signaling pathways (MAPK, Akt) via protein connection with specific phosphorylated tyrosine residue. This mechanism is a mechanism of receptor activity above cell growth, differentiation, suppression of cell death and the like, which is believed to be responsible for the high receptor expression in malignant tumors and malignant transformation of the tumor due to a local increase in the concentration of ligand.

Many types of malignant tumors associated with high expression of EGFR or HER2. You can specify, for example, breast cancer (20-30%), ovarian cancer (20-40%), non-small cell lung cancer (30-60%), colorectal cancer (40-80%), prostate cancer (10-60%), bladder cancer (30-60%), kidney cancer (20-40%), and the like. In addition, there is a correlation between receptor expression and prognosis, and the receptor expression is an adverse prognostic factor in breast cancer, non-small cell lung cancer and the like.

In recent years, clinical use gumanitarnogo antibodies against HER2 (Trastuzumab against HER2 high expressing breast cancer, a clinical trial is ntitle against EGFR and clinical trials of several low molecular weight inhibitors of receptor enzymes showed the effectiveness of these pharmaceuticals against HER2 or EGFR as a therapeutic pharmaceutical funds against cancer. In addition, these drugs exhibit an inhibitory effect on tumor growth in pre-clinical and clinical trials, they are known to cause inhibition of receptor enzyme activity and suppression below in the course of the reactions signaling pathways. Therefore, linking, inhibition of EGFR or HER2 kinase or inhibiting the activation of EGFR or HER2 kinase, is effective as a medicine against cancer.

As compounds inhibiting receptor tyrosine kinase, presents HER2/EGFR kinase, known condensed heterocyclic compounds (for example, WO97/13771, WO98/02437, WO00/44728), derivatives of hintline (for example, WO02/02552, WO01/98277, WO03/049740, WO03/050108), derivatives of thienopyrimidine (for example, WO03/053446), derivatives of aromatic azole (for example, WO98/03648, WO01/77107, WO03/031442) and the like, but as yet there is no inhibition of HER2 kinase substances presented on the market as a drug against cancer.

With regard to derivatives pyrrolo[3,2-d]pyrimidine, known as compounds with inhibiting the cell growth activity, the following compounds (Khim.-Farm. Zh., 1982, 16, 1338-1343; Collect. Czech. Chem. Commun., 2003, 68, 779-791):

As compounds with the activity of the receptor slapshot is incense, we know the following derived pyrrolo[3,2-d]pyrimidine (WO96/40142, WO98/23613):

In addition, with regard to derivatives of pyrazolo[4,3-d]pyrimidine, known derivatives 3,5,7-triple-substituted pyrazolo[4,3-d]pyrimidine as connections, providing inhibitory effect on CDK, inhibitory effect on cell growth and/or inducing effect on apoptosis (EP-A-1348707), and derivatives of 3-isopropylpyrazole[4,3-d]pyrimidine as compounds with inhibitory activity against CDK1/cycline B (Bioorganic & Medicinal Chemistry Letters, 2003, 13, 2989-2992). In addition, it is known about the synthesis of derivatives of 3-methylpyrazolo[4,3-d]pyrimidine (The Journal of Organic Chemistry, 1956, 21, 833-836).

Disclosure of the invention

The aim of the present invention is to provide compounds that provide excellent inhibitory effect on tyrosinekinase, which is non-lethal and highly satisfactory as a pharmaceutical product.

The authors of the present invention have conducted intensive studies and found that the compound represented by the following formula (I)and its salt (sometimes referred to herein as compound (I)) have excellent inhibitory effect on tyrosinekinase. Further research was completed by the present invention.

Thus, in accordance with the tvii with the present invention include:

[1] a compound represented by the formula:

where W represents C(R1or N,

A represents an optionally substituted aryl group or optionally substituted heteroaryl group,

X1 represents-NR3-Y1-, -O-, -S-, -SO-, -SO2- or-CHR3-where R3represents a hydrogen atom or optionally substituted aliphatic hydrocarbon group, or R3not necessarily associated with carbon atom or a heteroatom in the aryl group or the heteroaryl group represented by A, with the formation of optionally substituted ring structure, and

Y1represents a single bond or optionally substituted C1-4alkylene or optionally substituted-O-(C1-4alkylene)-,

R1represents a hydrogen atom or an optionally substituted group attached through a carbon atom, a nitrogen atom or an oxygen atom, and R2represents a hydrogen atom or an optionally substituted group attached through a carbon atom or a sulfur atom, or

R1and R2or R2and R3not necessarily related to education optionally substituted ring structure, provided that the compounds represented by the formula

excluded, or Ecosol,

[2] the prodrug compounds according to the above item [1],

[3] the compound according to above item [1], where W represents C(R1),

[4] the compound according to above item [3], where a represents an aryl group substituted by a group of the formula-Y2-B and optionally additionally substituted, where Y2represents a single bond, -O-, -O-(C1-3alkylene)-, -NH - or-S-, and represents an aryl group, a heterocyclic group, a C3-8cycloalkyl group, carbamoyl group, raidgroup, C6-18arylcarbamoyl group or a C6-18aryl-C1-4alkylcarboxylic group, each of which is optionally substituted,

[5] the compound according to above item [3], where R1represents a group of formula-X2-R4where X2represents a single bond, -NH - or-O-, and R4represents a hydrogen atom, cyano or C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, karbamoilnuyu group, C1-8alkylcarboxylic group, C3-8cycloalkyl group, C6-18aryl group, a C6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, heterocyclic group, a heterocycle-C1-4alkyl group, heterocy carbonyloxy group or a heterocycle-C 1-4alkylcarboxylic group, each of which is optionally substituted,

[6] the compound according to above item [3], where R2represents a hydrogen atom or a C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, karbamoilnuyu group, C1-8alkylcarboxylic group, C1-8alkylsulfonyl group, C3-8cycloalkyl group, C6-18aryl group, a C6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, C6-18arylsulfonyl group, heterocyclic group, a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted,

[7] the compound according to above item [3], where X1 represents-NR3-where R3represents a hydrogen atom or optionally substituted aliphatic hydrocarbon group,

[8] the compound according to above item [3], where a represents an aryl group substituted by a group of the formula-Y2-B and optionally additionally substituted, where Y2represents a single bond, -O-, -O-(C1-3alkylene)-, -NH - or-S-, and represents an aryl group, a heterocyclic group, a C3-8cyclol the ilen group, carbamoyl group, raidgroup, C6-18arylcarbamoyl group or a C6-18aryl-C1-4alkylcarboxylic group, each of which is optionally substituted;

R1represents a group of formula-X2-R4where X2represents a single bond, -NH - or-O-, and R4represents a hydrogen atom, cyano or C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, karbamoilnuyu group, C1-8alkylcarboxylic group, C3-8cycloalkyl group, C6-18aryl group, a C6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, heterocyclic group, a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted;

R2represents a hydrogen atom or a C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, karbamoilnuyu group, C1-8alkylcarboxylic group, C1-8alkylsulfonyl group, C3-8cycloalkyl group, C6-18aryl group, a C6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, C6-18and ylsulphonyl group, heterocyclic group, a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted; and

X1 represents-NR3-where R3represents a hydrogen atom or optionally substituted aliphatic hydrocarbon group,

[9] the compound according to above item [1], where W represents N,

[10] the compound according to above item [9], where a represents an aryl group substituted by a group of the formula-Y2-B and optionally additionally substituted, where Y2represents a single bond, -O-, -O-(C1-3alkylene)-, -NH - or-S-, and represents an aryl group, a heterocyclic group, a C3-8cycloalkyl group, carbamoyl group, raidgroup, C6-18arylcarbamoyl group or a C6-18aryl-C1-4alkylcarboxylic group, each of which is optionally substituted,

[11] the compound according to above item [9], where R2represents a hydrogen atom or a C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, karbamoilnuyu group, C1-8alkylcarboxylic group, C1-8alkylsulfonyl group, C3-8cycloalkyl group, C6-18aryl group, a C6-18aryl-C1-4and kilou group, C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, C6-18arylsulfonyl group, heterocyclic group, a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted,

[12] the compound according to above item [9], where X1 represents-NR3-where R3represents a hydrogen atom or optionally substituted aliphatic hydrocarbon group,

[13] the compound according to above item [9], where X1 represents-NR3-where R3represents a hydrogen atom or optionally substituted aliphatic hydrocarbon group;

But is an aryl group substituted by a group of the formula-Y2-B and optionally additionally substituted, where Y2represents a single bond, -O-, -O-(C1-3alkylene)-, -NH - or-S-, and represents an aryl group, a heterocyclic group, a C3-8cycloalkyl group, carbamoyl group, raidgroup, C6-18arylcarbamoyl group or a C6-18aryl-C1-4alkylcarboxylic group, each of which is optionally substituted;

R2represents a hydrogen atom or a C1-8alkyl group, a C2-8alkenylphenol group, C2-8Ala is niloy group, karbamoilnuyu group, C1-8alkylcarboxylic group, C1-8alkylsulfonyl group, C3-8cycloalkyl group, C6-18aryl group, a C6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, C6-18arylsulfonyl group, heterocyclic group, a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted,

[14] the compound according to above item [9], where X1 represents-NR3-;

But is an aryl group substituted by a group of the formula-Y2-B and optionally additionally substituted, where Y2represents a single bond, -O-, -O-(C1-3alkylene)-, -NH - or-S-, and represents an aryl group, a heterocyclic group, a C3-8cycloalkyl group, carbamoyl group, raidgroup, C6-18arylcarbamoyl group or a C6-18aryl-C1-4alkylcarboxylic group, each of which is optionally substituted; and

R2and R3related to education optionally substituted ring structure,

[15] the compound represented by the formula:

where R1arepresents a hydrogen atom or long is Ino substituted group, attached via a carbon atom, a nitrogen atom or an oxygen atom

R2ais an optionally substituted group attached through a carbon atom or a sulfur atom, or

R1aand R2aor R2aand R3anot necessarily related to education optionally substituted ring structure,

R3arepresents a hydrogen atom or optionally substituted aliphatic hydrocarbon group, or

R3anot necessarily linked to the carbon atom of the adjacent phenyl group with the formation of optionally substituted ring structure,

Barepresents an optionally substituted benzene ring, and

Carepresents an optionally substituted C6-18aryl group, or its salt,

[16] the compound represented by the formula:

where R1brepresents a hydrogen atom or an optionally substituted group attached through a carbon atom, a nitrogen atom or an oxygen atom

R2bis an optionally substituted group attached through a carbon atom or a sulfur atom, or

R1band R2bor R2band R3bnot necessarily related to education optionally substituted ring structure,

R3brepresents a hydrogen atom or optional is entrusted substituted aliphatic hydrocarbon group, or

R3bnot necessarily linked to the carbon atom of the adjacent phenyl group with the formation of optionally substituted ring structure,

Bbrepresents an optionally substituted benzene ring,

Cbrepresents an optionally substituted C6-18aryl group, and

Zbrepresents an optionally substituted C1-3alkylenes group, or its salt,

[17] the compound represented by the formula:

where R1crepresents a hydrogen atom or an optionally substituted group attached through a carbon atom, a nitrogen atom or an oxygen atom

R2cis an optionally substituted group attached through a carbon atom or a sulfur atom, or

R1cand R2cor R2cand R3cnot necessarily related to education optionally substituted ring structure,

R3crepresents a hydrogen atom or optionally substituted aliphatic hydrocarbon group, or

R3cnot necessarily linked to the carbon atom of the adjacent phenyl group with the formation of optionally substituted ring structure,

Bcrepresents an optionally substituted benzene ring, and

Ccrepresents an optionally substituted heterocyclics the second group, or its salt,

[18] the compound represented by the formula:

where R1drepresents a hydrogen atom or an optionally substituted group attached through a carbon atom, a nitrogen atom or an oxygen atom

R2dis an optionally substituted group attached through a carbon atom or a sulfur atom, or

R1dand R2dor R2dand R3dnot necessarily related to education optionally substituted ring structure,

R3drepresents a hydrogen atom or optionally substituted aliphatic hydrocarbon group, or

R3dnot necessarily linked to the carbon atom of the adjacent phenyl group with the formation of optionally substituted ring structure,

Bdrepresents an optionally substituted benzene ring,

Cdrepresents an optionally substituted heterocyclic group, and

Zdrepresents an optionally substituted C1-3alkylenes group, or its salt,

[19] the compound represented by the formula:

where R2eis an optionally substituted group attached through a carbon atom or a sulfur atom, or

R2eand R3enot necessarily related to education optional C is displaced ring structure

R3erepresents a hydrogen atom or optionally substituted aliphatic hydrocarbon group, or

R3enot necessarily linked to the carbon atom of the adjacent phenyl group with the formation of optionally substituted ring structure,

Berepresents an optionally substituted benzene ring, and

Cerepresents an optionally substituted C6-18aryl group, or its salt,

[20] the compound represented by the formula:

where R2fis an optionally substituted group attached through a carbon atom or a sulfur atom, or

R2fand R3fnot necessarily related to education optionally substituted ring structure,

R3frepresents a hydrogen atom or optionally substituted aliphatic hydrocarbon group, or

R3fnot necessarily linked to the carbon atom of the adjacent phenyl group with the formation of optionally substituted ring structure,

Bfrepresents an optionally substituted benzene ring,

Cfrepresents an optionally substituted C6-18aryl group, and

Zfrepresents an optionally substituted C1-3alkylenes group, or its salt,

[21] the connection, as the e by the formula:

where R2gis an optionally substituted group attached through a carbon atom or a sulfur atom, or

R2gand R3gnot necessarily related to education optionally substituted ring structure,

R3grepresents a hydrogen atom or optionally substituted aliphatic hydrocarbon group, or

R3gnot necessarily linked to the carbon atom of the adjacent phenyl group with the formation of optionally substituted ring structure,

Bgrepresents an optionally substituted benzene ring, and

Cgrepresents an optionally substituted heterocyclic group, or its salt,

[22] (i) 2-{2-[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethoxy}ethanol

(ii) 2-{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethoxy}ethanol

(iii) N-{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}-3-hydroxy-3-methylbutanoic,

(iv) N-{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}-2-(methylsulphonyl)ndimethylacetamide,

(v) N-{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}-2-methyl-2-(methylsulphonyl)propanamide,

(vi) 5-{2-[2-(tert-butylsulfonyl)ethoxy]ethyl}-N-{3-chloro--[3-(trifluoromethyl)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine,

(vii) 2-(methylsulphonyl)-N-{2-[4-({3-methyl-4-[3-(triptoreline)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}acetamide", she

(viii) N-[2-(4-{[3-chloro-4-(3-chlorophenoxy)phenyl]amino}-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethyl]-2-(methylsulphonyl)ndimethylacetamide or

(ix) N-{2-[4-({3-chloro-4-[3-(triptoreline)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}-2-(methylsulphonyl)ndimethylacetamide or salt of any of them,

[23] the method of obtaining the compound represented by the formula:

wherein each symbol is as defined in the above item [1], or its salt, which comprises the interaction of the compounds represented by the formula:

where L represents a leaving group and other symbols are as defined in the above item [1]or its salt with a compound represented by the formula:

where G represents a hydrogen atom or a metal atom, and other symbols are as defined in the above item [1], or its salt,

[24] a pharmaceutical agent containing the compound represented by the formula:

where W represents C(R1or N,

A represents an optionally substituted aryl group or optionally substituted heteroaryl group,

X1 represents-NR3-Y1-, -O-, -S-, -SO-, -SO2- or-CHR3-where R3represents a hydrogen atom or optionally substituted aliphatic hydrocarbon group, or R3not necessarily associated with carbon atom or a heteroatom in the aryl group or the heteroaryl group represented by A, with the formation of optionally substituted ring structure, and Y1represents a single bond or optionally substituted C1-4alkylene or optionally substituted-O-(C1-4alkylene)-,

R1represents a hydrogen atom or an optionally substituted group attached through a carbon atom, a nitrogen atom or an oxygen atom, and

R2represents a hydrogen atom or an optionally substituted group attached through a carbon atom or a sulfur atom, or

R1and R2or R2and R3not necessarily related to education optionally substituted ring structure, provided that the compounds represented by the formula

excluded, or its salt or prodrug,

[25] the pharmaceutical agent according to the above item [24], which is a tyrosine kinase inhibitor,

[26] the pharmaceutical agent according to the above item [24], which is a tool for prevention is or cancer treatment

[27] the pharmaceutical agent according to the above item [26], where the cancer is a breast cancer, prostate cancer, lung cancer, pancreatic cancer or kidney cancer,

[28] a method for preventing or treating cancer in a mammal, comprising an introduction to the specified mammal an effective amount of the compound represented by the formula:

where W represents C(R1or N,

A represents an optionally substituted aryl group or optionally substituted heteroaryl group,

X1 represents-NR3-Y1-, -O-, -S-, -SO-, -SO2- or-CHR3-where R3represents a hydrogen atom or optionally substituted aliphatic hydrocarbon group, or R3not necessarily associated with carbon atom or a heteroatom in the aryl group or the heteroaryl group represented by A, with the formation of optionally substituted ring structure, and y1represents a single bond or optionally substituted C1-4alkylene or optionally substituted-O-(C1-4alkylene)-,

R1represents a hydrogen atom or an optionally substituted group attached through a carbon atom, a nitrogen atom or an oxygen atom, and

R2represents a hydrogen atom or neoba is consequently substituted group, attached via a carbon atom or a sulfur atom, or

R1and R2or R2and R3not necessarily related to education optionally substituted ring structure, provided that the compounds represented by the formula

excluded, or its salt or prodrug,

[29] the use of compounds represented by the formula:

where W represents C(R1or N,

A represents an optionally substituted aryl group or optionally substituted heteroaryl group,

X1 represents-NR3-Y1-, -O-, -S-, -SO-, -SO2- or-CHR3-where R3represents a hydrogen atom or optionally substituted aliphatic hydrocarbon group, or R3not necessarily associated with carbon atom or a heteroatom in the aryl group or the heteroaryl group represented by A, with the formation of optionally substituted ring structure, and y1represents a single bond or optionally substituted C1-4alkylene or optionally substituted-O-(C1-4alkylene)-,

R1represents a hydrogen atom or an optionally substituted group attached through a carbon atom, a nitrogen atom or an oxygen atom, and

R2is an atom ogorodili optionally substituted group attached via a carbon atom or a sulfur atom, or

R1and R2or R2and R3not necessarily related to education optionally substituted ring structure, provided that the compounds represented by the formula

excluded, or its salts, or prodrugs for the manufacture of products for the prevention or treatment of cancer, and the like.

In addition, in accordance with the present invention include:

[30] the compound according to above item [15], where

R2arepresents a

(i) C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, C1-8alkylcarboxylic group, C1-8alkylsulfonyl group, C3-8cycloalkyl group, C6-18aryl group, a C6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, C6-18arylsulfonyl group, heterocyclic group, a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted by 1-5 substituents selected from group (group T substituents), consisting of

(a) halogen,

(b) oxo,

(c) optionally halogenated C1-4of alkyl,

(d) -(CH )m-Q,

(e) -(CH2)m-Z1-(optionally halogenated C1-4the alkyl),

(f) -(CH2)m-Z1-C3-8cycloalkyl,

(g) -(CH2)m-Z2-(CH2)n-Q,

(h) -(CH2)m-Z2-(CH2)n-Z1-(optionally halogenated C1-4the alkyl),

(i) -(CH2)m-Z2-(CH2)n-Z1-C3-8cycloalkyl,

(j) -(CH2)m-Z1-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom),

(k) -(CH2)m-Z2-C1-4alkoxy and

(l) -(CH2)m-Z2-(CH2)n-Z1-(CH2)n-Z1-C1-4of alkyl,

where m is an integer from 0 to 4,

n is an integer from 1 to 4

Q represents hydroxy, carboxy, cyano, nitro, -NR6R7, -CONR6R7, -OCONH2or-SO2NR6R7,

Z1 represents-O-, -CO-, -C(OH)R8-, -C(=N-OR8)-, -S-, -SO-, -SO2-, -N(COR8)-, -N(CO2R9)-, -N(SO2R9)-, -CO-O-, -O-CO-, -CO-NR8-, -NR8-CO-, -NR8-CO2-, -NR8-CO-NH-, -NR8-SO2- or-NR8-C(=NH)NH-,

Z2 represents-O-, -CO-, -C(OH)R8-, -C(=N-OR8)-, -S-, -SO-, -SO2-, -NR8-, -N(COR8)-, -N(CO2R9)-, -N(SO2R9)-, -CO-O-, -O-CO-, -CO-NR8-, -NR8-CO-, -NR8-CO2-, -NR8-CO-NH-, -NR8-C(=NH)-NH-, -NR8-SO2- or-SO2-NR8-,

(CH2)mand (CH2)noptionally substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4of alkyl and hydroxy, and when m or n is not less than 2, a subset-CH2CH2groups (CH2)mand (CH2)noptionally replaced by-CH=CH - or-C≡C-,

R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, or R6and R7related to education, together with the nitrogen atom, a 3-8-membered saturated or unsaturated aliphatic heterocyclic group,

R8represents a hydrogen atom or a C1-4alkyl group, and

R9represents a C1-4alkyl group, or

(ii) karbamoilnuyu group, optionally containing 1 or 2 C1-8alkyl group optionally substituted by substituent(s)selected(s) from the group T substituents where indicated carnemolla group contains two Deputy, which may not form, together with the adjacent nitrogen atom, to 8-membered saturated or unsaturated aliphatic heterocyclic group, optionally substituted by substituent(s)selected(s) from the group T substituents,

[31] the compound according to above item [15], where

Barepresents a benzene ring, optionally substituted by 1-4 substituents selected from halogen, C1-4of alkyl, hydroxy-C1-4the alkyl and C1-4alkyloxy;

Carepresents a phenyl group, optionally substituted by 1-5 substituents selected from the

(i) halogen,

(ii) optionally halogenated C1-4of alkyl,

(iii) hydroxy-C1-4of alkyl,

(iv) heterocycle-C1-4the alkyl (preferably 5-8-membered heterocycle-C1-4of alkyl, where the specified 5-8-membered heterocycle contains 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, such as imidazolyl, triazolyl and the like),

(v) optionally halogenated C1-4alkyloxy,

(vi) C1-4alkylcarboxylic,

(vii) cyano,

(viii) carbamoyl, optionally substituted C1-8the alkyl, and

(ix) C1-4alkoxycarbonyl;

R1arepresents a

(i) a hydrogen atom,

(ii) a cyano or

(iii) C1-4alkyl group or a C2-4alkenylphenol group, each of which is optionally substituted by-NR8-CO-(CH2)n-NR6R7where n is an integer from 1 to 4, R6and Rsup> 7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, R8represents a hydrogen atom or a C1-4alkyl group, and when n is not less than 2, a subset-CH2CH2group (CH2)noptionally replaced by-CH=CH-; and

R2arepresents a C1-8alkyl group, a C2-8alkenylphenol group or a C2-8alkylamino group, each of which is optionally substituted by substituent(s)selected(s)

(a) hydroxy,

(b) carboxy,

(c) cyano,

(d) optionally halogenated C1-4alkyloxy,

(e) -O-(CH2)n-OH,

(f) -O-(CH2)n-O-CO-NH2,

(g) -O-(CH2)n-O-(optionally halogenated C1-4the alkyl),

(h) -O-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(i) -O-(CH2)n-SO2-C6-18aryl,

(j) -O-(CH2)n-SO2-(CH2)n-OH,

(k) -O-(CH2)n-NR8-CO-C1-4of alkyl,

(l) -O-(CH2)n-NR8-CO-(CH2)n-SO2-C1-4of alkyl,

(m) -O-(CH2)n-NR8-SO2-(optionally halogenated C1-4the alkyl),

(n) -CO-NR8-(CH2)n-OH,

(o) -CO-NR8-(CH2)n-SO2-(optionally halogenated C1-4and the Qila),

(p) -CO-NR8-O-C1-4of alkyl,

(q) -NR6R7,

(r) -NR8-(CH2)n-OH,

(s) -NR8-(CH2)n-SO2-C1-4of alkyl,

(t) -NR8-CO-(optionally halogenated C1-4the alkyl),

(u) -NR8-CO-(CH2)n-OH,

(v) -NR8-CO-(CH2)n-CN

(w) -NR8-CO-(CH2)n-NR6R7,

(x) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(y) -NR8-CO-(CH2)n-SO-(optionally halogenated C1-4the alkyl),

(z) -NR8-CO-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(aa) -NR8-CO-(CH2)n-SO2-C3-8cycloalkyl,

(bb) -NR8-CO-(CH2)n-NR8-SO2-C1-4of alkyl,

(cc) -NR8-CO2-(CH2)n-SO2-C1-4of alkyl,

(dd) -NR8-CO-NH-(CH2)n-SO2-C1-4of alkyl,

(ee) -NR8-CO-NH-O-C1-4of alkyl,

(ff) -NR8-CO-NH-(CH2)n-O-C1-4of alkyl,

(gg) -NR8-C(=NH)-NH-C1-4of alkyl,

(hh) -NR8-SO2-(CH2)n-SO2-C1-4of alkyl,

(ii) -S-(CH2)n-OH,

(jj) -SO-(CH2)n-OH,

(kk) -SO2-(CH2)n-OH, and

(ll) -NR8-CO-(optionally substituted heterocyclic group) (this heterocyclic group preferably having presented the em a 5-8-membered heterocyclic group, containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, which is optionally substituted by substituent(s)selected(s) hydroxy, C1-4the alkyl, optionally oxidized With1-4alkylthio, -CO-C1-4of alkyl, -CO-O-C1-4of alkyl, -CO-NH-C1-4of alkyl, -CONH2, -SO2-C1-4of alkyl, -SO2-NH-C1-4of alkyl, -SO2NH2and the like),

where n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, R8represents a hydrogen atom or a C1-4alkyl group, a group (CH2)noptionally substituted halogenated C1-4the alkyl or hydroxy, and when n is not less than 2, a subset-CH2CH2group (CH2)noptionally replaced by-CH=CH-;

R3arepresents a hydrogen atom or a C1-6alkyl group; or

R1aand R2anot necessarily related to educationor; or

R2aand R3anot necessarily related to the formation of C2-4alkylene, optionally substituted aminogroups,

particularly preferably, R2arepresents a C1-8alkyl group, a C2-8alkenylphenol group and the and C 2-8alkylamino group (in particular, C1-8alkyl group), each of which is optionally substituted by substituent(s)selected(s)

(a) hydroxy,

(b) carboxy,

(c) cyano,

(d) optionally halogenated C1-4alkyloxy,

(e) -O-(CH2)n-OH (where the group (CH2)noptionally substituted by hydroxy),

(f) -O-(CH2)n-O-CO-NH2,

(g) -O-(CH2)n-O-(optionally halogenated C1-4the alkyl),

(h) -O-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(i) -O-(CH2)n-SO2-C6-18aryl,

(j) -O-(CH2)n-SO2-(CH2)n-OH,

(k) -O-(CH2)n-NR8-CO-C1-4of alkyl,

(l) -O-(CH2)n-NR8-CO-(CH2)n-SO2-C1-4of alkyl,

(m) -O-(CH2)n-NR8-SO2-(optionally halogenated C1-4the alkyl),

(n) -CO-NR8-(CH2)n-OH,

(o) -CO-NR8-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(p) -CO-NR8-O-C1-4of alkyl,

(q) -NR6R7,

(r) -NR8-(CH2)n-OH,

(s) -NR8-(CH2)n-SO2-C1-4of alkyl,

(t) -NR8-CO-(optionally halogenated C1-4the alkyl),

(u) -NR8-CO-(CH2)n-OH (where the group (CH2)n optionally substituted by optionally halogenated C1-4the alkyl or hydroxy),

(v) -NR8-CO-(CH2)n-CN

(w) -NR8-CO-(CH2)n-NR6R7(when n is not less than 2, a subset-CH2CH2group (CH2)noptionally replaced by-CH=CH-),

(x) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(y) -NR8-CO-(CH2)n-SO-(optionally halogenated C1-4the alkyl),

(z) -NR8-CO-(CH2)n-SO2-(optionally halogenated C1-4the alkyl) (where the group (CH2)noptionally substituted C1-4by alkyl),

(aa) -NR8-CO-(CH2)n-SO2-C3-8cycloalkyl,

(bb) -NR8-CO-(CH2)n-NR8-SO2-C1-4of alkyl,

(cc) -NR8-CO2-(CH2)n-SO2-C1-4of alkyl,

(dd) -NR8-CO-NH-(CH2)n-SO2-C1-4of alkyl,

(ee) -NR8-CO-NH-O-C1-4of alkyl,

(ff) -NR8-CO-NH-(CH2)n-O-C1-4of alkyl,

(gg) -NR8-C(=NH)-NH-C1-4of alkyl,

(hh) -NR8-SO2-(CH2)n-SO2-C1-4of alkyl,

(ii) -S-(CH2)n-OH,

(jj) -SO-(CH2)n-OH,

(kk) -SO2-(CH2)n-OH, and

(ll) -NR8-CO-(optionally substituted heterocyclic group) (this heterocyclic group is preferably pre which is a 5-8-membered heterocyclic group, containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, which is optionally substituted by substituent(s)selected(s) hydroxy, C1-4the alkyl, optionally oxidized C1-4alkylthio, -CO-C1-4of alkyl, -CO-O-C1-4of alkyl, -CO-NH-C1-4of alkyl, -CONH2, -SO2-C1-4of alkyl, -SO2-NH-C1-4of alkyl, -SO2NH2and the like),

where n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, R8represents a hydrogen atom or a C1-4alkyl group,

[32] the compound according to above item [15], where

Barepresents a benzene ring, optionally substituted by 1-4 substituents selected from halogen and optionally halogenated C1-4of alkyl;

Carepresents a phenyl group substituted by 1-5 substituents selected from the

(i) halogen,

(ii) optionally halogenated C1-4of alkyl,

(iii) hydroxy-C1-4of alkyl,

(iv) heterocycle-C1-4the alkyl (preferably 5-8-membered heterocycle-C1-4of alkyl, where the specified 5-8-membered heterocycle contains 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized CE atom is s, such as imidazolyl and the like),

(v) optionally halogenated C1-4alkyloxy,

(vi) cyano, and

(vii) carbamoyl, optionally substituted C1-8by alkyl;

R1arepresents a hydrogen atom;

R2arepresents a C1-8alkyl group, a C2-8alkenylphenol group or a C2-8alkylamino group, each of which is substituted by substituent(s)selected(s)

(a) hydroxy,

(b) optionally halogenated C1-4alkyloxy,

(c) -O-(CH2)n-OH,

(d) -O-(CH2)n-O-CO-NH2,

(e) -O-(CH2)n-O-C1-4of alkyl,

(f) -O-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(g) -O-(CH2)n-SO2-C6-18aryl,

(h) -O-(CH2)n-SO2-(CH2)n-OH,

(i) -O-(CH2)n-NR8-SO2-(optionally halogenated C1-4the alkyl),

(j) -CO-NR8-(CH2)n-OH,

(k) -CO-NR8-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(l) -NR6R7,

(m) -NR8-(CH2)n-OH,

(n) -NR8-(CH2)n-SO2-C1-4of alkyl,

(o) -NR8-CO-(CH2)n-OH,

(p) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(q) -NR8-CO-(CH2)n-SO-(optionally halogenated what about C 1-4the alkyl),

(r) -NR8-CO-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(s) -NR8-CO-(CH2)n-SO2-C3-8cycloalkyl,

(t) -NR8-CO2-(CH2)n-SO2-C1-4of alkyl,

(u) -NR8-CO-NH-(CH2)n-SO2-C1-4of alkyl,

(v) -NR8-SO2-(CH2)n-SO2-C1-4of alkyl,

(w) -S-(CH2)n-OH,

(x) -SO-(CH2)n-OH,

(y) -SO2-(CH2)n-OH, and

(z) -NR8-CO-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, which is optionally substituted by substituent(s)selected(s) hydroxy, C1-4the alkyl, optionally oxidized C1-4alkylthio, -CO-C1-4of alkyl, -CO-NH-C1-4of alkyl, -CONH2, -SO2-C1-4of alkyl, -SO2-NH-C1-4of alkyl, -SO2NH2and the like),

where n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, R8represents a hydrogen atom or a C1-4alkyl group and the group (CH2) optionally substituted C1-4the alkyl or hydroxy;

R3arepresents a hydrogen atom or a C1-6alkyl group; or

R1aand R2anot necessarily related to educationor; or

R2aand R3anot necessarily related to the formation of C2-4alkylene,

particularly preferably, R2arepresents a C1-8alkyl group, a C2-8alkenylphenol group or a C2-8alkylamino group (in particular, C1-8alkyl group), each of which is substituted by substituent(s)selected(s)

(a) hydroxy,

(b) optionally halogenated C1-4alkyloxy,

(c) -O-(CH2)n-OH (where the group (CH2)noptionally substituted by hydroxy),

(d) -O-(CH2)n-O-CO-NH2,

(e) -O-(CH2)n-O-C1-4of alkyl,

(f) -O-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(g) -O-(CH2)n-SO2-C6-18aryl,

(h) -O-(CH2)n-SO2-(CH2)n-OH,

(i) -O-(CH2)n-NR8-SO2-(optionally halogenated C1-4the alkyl),

(j) -CO-NR8-(CH2)n-OH,

(k) -CO-NR8-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(l) -NR6R7,

(m) -NR -(CH2)n-OH,

(n) -NR8-(CH2)n-SO2-C1-4of alkyl,

(o) -NR8-CO-(CH2)n-OH (where the group (CH2)noptionally substituted C1-4by alkyl),

(p) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(q) -NR8-CO-(CH2)n-SO-(optionally halogenated C1-4the alkyl),

(r) -NR8-CO-(CH2)n-SO2-(optionally halogenated C1-4the alkyl) (where the group (CH2)noptionally substituted C1-4by alkyl),

(s) -NR8-CO-(CH2)n-SO2-C3-8cycloalkyl,

(t) -NR8-CO2-(CH2)n-SO2-C1-4of alkyl,

(u) -NR8-CO-NH-(CH2)n-SO2-C1-4of alkyl,

(v) -NR8-SO2-(CH2)n-SO2-C1-4of alkyl,

(w) -S-(CH2)n-OH,

(x) -SO-(CH2)n-OH,

(y) -SO2-(CH2)n-OH, and

(z) -NR8-CO-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, which is optionally substituted by substituent(s)selected(s) hydroxy, C1-4the alkyl, optionally oxidized C1-4alkylthio, -CO-C1-4 of alkyl, -CO-NH-C1-4of alkyl, -CONH2, -SO2-C1-4of alkyl, -SO2-NH-C1-4of alkyl, -SO2NH2and the like),

where n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, and R8represents a hydrogen atom or a C1-4alkyl group,

[33] the compound according to above item [31], where

R2arepresents (i) C5-8alkyl group, a substituted hydroxy,

(ii) C1-8alkyl group substituted by substituent(s)selected(s)

(a) halogenated C1-4alkyloxy,

(b) -O-(CH2)n-OH,

(c) -O-(CH2)n-O-CO-NH2,

(d) -O-(CH2)n-O-(optionally halogenated C1-4the alkyl),

(e) -O-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(f) -O-(CH2)n-SO2-C6-18aryl,

(g) -O-(CH2)n-NR8-SO2-(optionally halogenated C1-4the alkyl),

(h) -CO-NR8-(CH2)n-OH,

(i) -CO-NR8-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(j) -NR8-(CH2)n-SO2-C1-4of alkyl,

(k) -NR8-CO-(CH2)n-OH,

(l) -NR8-CO-(CH2)n-O-C1-4of alkyl,

m) -NR 8-CO-(CH2)n-SO-(optionally halogenated C1-4the alkyl),

(n) -NR8-CO-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(o) -NR8-CO-(CH2)n-SO2-C3-8cycloalkyl,

(p) -NR8-CO2-(CH2)n-SO2-C1-4of alkyl,

(q) -NR8-CO-NH-(CH2)n-SO2-C1-4of alkyl,

(r) -NR8-SO2-(CH2)n-SO2-C1-4of alkyl,

(s) -S-(CH2)n-OH,

(t) -SO-(CH2)n-OH,

(u) -SO2-(CH2)n-OH, and

(v) -NR8-CO-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, which is optionally substituted by substituent(s)selected(s) hydroxy, C1-4the alkyl, optionally oxidized C1-4alkylthio, -CO-C1-4of alkyl, -CO-NH-C1-4of alkyl, -CONH2, -SO2-C1-4of alkyl, -SO2-NH-C1-4of alkyl, -SO2NH2and the like),

where n is an integer from 1 to 4, R8represents a hydrogen atom or a C1-4alkyl group and the group (CH2)noptionally substituted C1-4the alkyl or hydroxy,

iii) C 2-8alkenylphenol group, optionally substituted hydroxy, or

(iv) C2-8alkylamino group, optionally substituted hydroxy,

particularly preferably, R2arepresents a

(i) C5-8alkyl group, a substituted hydroxy,

(ii) C1-8alkyl group substituted by substituent(s)selected(s)

(a) halogenated C1-4alkyloxy,

(b) -O-(CH2)n-OH (where the group (CH2)noptionally substituted by hydroxy),

(c) -O-(CH2)n-O-CO-NH2,

(d) -O-(CH2)n-O-(optionally halogenated C1-4the alkyl),

(e) -O-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(f) -O-(CH2)n-SO2-C6-18aryl,

(g) -O-(CH2)n-NR8-SO2-(optionally halogenated C1-4the alkyl),

(h) -CO-NR8-(CH2)n-OH,

(i) -CO-NR8-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(j) -NR8-(CH2)n-SO2-C1-4of alkyl,

(k) -NR8-CO-(CH2)n-OH (where the group (CH2)noptionally substituted C1-4by alkyl),

(l) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(m) -NR8-CO-(CH2)n-SO-(optionally halogenated C1-4the alkyl),

(n) -NR8-CO-(CH2)n-SOsub> 2-(optionally halogenated C1-4the alkyl) (where the group (CH2)noptionally substituted C1-4by alkyl),

(o) -NR8-CO-(CH2)n-SO2-C3-8cycloalkyl,

(p) -NR8-CO2-(CH2)n-SO2-C1-4of alkyl,

(q) -NR8-CO-NH-(CH2)n-SO2-C1-4of alkyl,

(r) -NR8-SO2-(CH2)n-SO2-C1-4of alkyl,

(s) -S-(CH2)n-OH,

(t) -SO-(CH2)n-OH,

(u) -SO2-(CH2)n-OH, and

(v) -NR8-CO-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, which is optionally substituted by substituent(s)selected(s) hydroxy, C1-4the alkyl, optionally oxidized C1-4alkylthio, -CO-C1-4of alkyl, -CO-NH-C1-4of alkyl, -CONH2, -SO2-C1-4of alkyl, -SO2-NH-C1-4of alkyl, -SO2NH2and the like),

where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group,

(iii) C2-8alkenylphenol group, optionally substituted hydroxy, or

(iv) C2-8alkylamino group, optional Zam is protected hydroxy,

[34] the compound according to above item [16], where

R2brepresents (i) C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, C1-8alkylcarboxylic group, C1-8alkylsulfonyl group, C3-8cycloalkyl group, C6-18aryl group, a C6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, C6-18arylsulfonyl group, heterocyclic group, a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted by 1-5 substituents selected from group (group T substituents), consisting of

(a) halogen,

(b) oxo,

(c) optionally halogenated C1-4of alkyl,

(d) -(CH2)m-Q,

(e) -(CH2)m-Z1-(optionally halogenated C1-4the alkyl),

(f) -(CH2)m-Z1-C3-8cycloalkyl,

(g) -(CH2)m-Z2-(CH2)n-Q,

(h) -(CH2)m-Z2-(CH2)n-Z1-(optionally halogenated C1-4the alkyl),

(i) -(CH2)m-Z2-(CH2)n-Z1-C3-8cycloalkyl,

(j) -(CH2)m-Z1-(optional substituted hetero Klionsky group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group, containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom),

(k) -(CH2)m-Z2-C1-4alkoxy and

(l) -(CH2)m-Z2-(CH2)n-Z1-(CH2)n-Z1-C1-4of alkyl,

where m is an integer from 0 to 4, n is an integer from 1 to 4

Q represents hydroxy, carboxy, cyano, nitro, -NR6R7, -CONR6R7, -OCONH2or-SO2NR6R7,

Z1 represents-O-, -CO-, -C(OH)R8-, -C(=N-OR8)-, -S-, -SO-, -SO2-, -N(COR8)-, -N(CO2R9)-, -N(SO2R9)-, -CO-O-, -O-CO-, -CO-NR8-, -NR8-CO-, -NR8-CO2-, -NR8-CO-NH-, -NR8-SO2- or-NR8-C(=NH)-NH-,

Z2 represents-O-, -CO-, -C(OH)R8-, -C(=N-OR8)-, -S-, -SO-, -SO2-, -NR8-, -N(COR8)-, -N(CO2R9)-, -N(SO2R9)-, -CO-O-, -O-CO-, -CO-NR8-, -NR8-CO-, -NR8-CO2-, -NR8-CO-NH-, -NR8-C(=NH)-NH-, -NR8-SO2- or-SO2-NR8-,

(CH2)mand (CH2)noptionally substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4of alkyl and hydroxy, and when m or n is not less than 2, a subset-CH2CH2groups (CH2)mand (CH2)noptionally replaced by-CH=CH - or-C≡C-,

R6R 7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, or R6and R7related to education, together with the nitrogen atom, a 3-8-membered saturated or unsaturated aliphatic heterocyclic group,

R8represents a hydrogen atom or a C1-4alkyl group, and R9represents a C1-4alkyl group, or

(ii) karbamoilnuyu group, optionally containing 1 or 2 C1-8alkyl group optionally substituted by substituent(s)selected(s) from the group T substituents,

where carnemolla group contains two deputies and they optionally form, together with the adjacent nitrogen atom, a 3-8-membered saturated or unsaturated aliphatic heterocyclic group, optionally substituted by substituent(s)selected(s) from the group T substituents,

[35] the compound according to above item [16], where

Bbrepresents a benzene ring, optionally substituted with halogen;

Cbrepresents a phenyl group, optionally substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4the alkyl and cyano;

R1brepresents (i) hydrogen atom or (ii) C2-4alkenylphenol group, optionally substituted hydroxy;

R2b represents a

(i) C1-8alkyl group optionally substituted by substituent(s)selected(s)

(a) halogen,

(b) hydroxy,

(c) C1-4alkyloxy,

(d) -O-(CH2)n-OH,

(e) -O-(CH2)n-O-C1-4of alkyl,

(f) -CO-NR8-(CH2)n-OH,

(g) -NR6R7and

(h) -NR8-(CH2)n-OH,

where n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, and R8represents a hydrogen atom or a C1-4alkyl group,

(ii) C6-18aryl-C1-4alkyl group optionally substituted by substituent(s)selected(s)

(a) C1-4the alkyl, optionally containing hydroxy,

(b) carboxy,

(c) C1-4alkoxycarbonyl,

(d) 5-8-membered heterocultural containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, which optionally has substituent(s)selected(e) of hydroxy and C1-4of alkyl, and

(e) C1-4allylcarbamate, optionally containing substituent(s)selected(e) of hydroxy and carbamoyl,

(iii) C6-18arylcarbamoyl group, optionally substituted C1-4alkoxy,

(iv) C6-18arylsulfonyl group, optionally substituted C1-4Alcock and, or

(v) 5-8-membered heterocycle-C1-4alkyl group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, which is optionally substituted by substituent(s)selected(s)

(a) carboxy, and

(b) C1-4alkoxycarbonyl;

R3brepresents a hydrogen atom or a C1-6alkyl group; or

R2band R3bnot necessarily related to the formation of C2-4alkylene; and

Zbrepresents a C1-3alkylenes group,

[36] the compound according to above item [16], where

Bbrepresents a benzene ring, optionally substituted with halogen;

Cbrepresents a phenyl group, optionally substituted by 1-5 substituents selected from halogen and optionally halogenated C1-4of alkyl;

R1brepresents a hydrogen atom;

R2brepresents a C1-8alkyl group optionally substituted by substituent(s)selected(s)

(a) hydroxy,

(b) -O-(CH2)n-OH,

(c) -O-(CH2)n-O-C1-4of alkyl,

(d) -CO-NR8-(CH2)n-OH,

(e) -NR6R7and

(f) -NR8-(CH2)n-OH,

where n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4al the strong group, and R 8represents a hydrogen atom or a C1-4alkyl group;

R3brepresents a hydrogen atom or a C1-6alkyl group; and

Zbrepresents a C1-3alkylenes group,

[37] the compound according to above item [36], where

Bbrepresents a benzene ring, optionally substituted with halogen;

Cbrepresents a phenyl group, optionally substituted by 1-5 substituents selected from halogen and optionally halogenated C1-4of alkyl;

R1brepresents a hydrogen atom;

R2brepresents a C1-8alkyl group substituted by substituent(s)selected(s)

(a) -O-(CH2)n-OH,

(b) -O-(CH2)n-O-C1-4the alkyl and

(c) -CO-NR8-(CH2)n-OH,

where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group;

R3brepresents a hydrogen atom or a C1-6alkyl group; and

Zbrepresents a methylene group,

[38] the compound according to above item [17], where

R2crepresents (i) C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, C1-8alkylcarboxylic group, C1-8alkylsulfonyl group, C3-8cycloalkyl is the Rupp, C6-18aryl group, a C6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, C6-18arylsulfonyl group, heterocyclic group, a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted by 1-5 substituents selected from group (group T substituents), consisting of

(a) halogen,

(b) oxo,

(c) optionally halogenated C1-4of alkyl,

(d) -(CH2)m-Q,

(e) -(CH2)m-Z1-(optionally halogenated C1-4the alkyl),

(f) -(CH2)m-Z1-C3-8cycloalkyl,

(g) -(CH2)m-Z2-(CH2)n-Q,

(h) -(CH2)m-Z2-(CH2)n-Z1-(optionally halogenated C1-4the alkyl),

(i) -(CH2)m-Z2-(CH2)n-Z1-C3-8cycloalkyl,

(j) -(CH2)m-Z1-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom),

(k) -(CH2)m-Z2-C1-4 alkoxy and

(l) -(CH2)m-Z2-(CH2)n-Z1-(CH2)n-Z1-C1-4of alkyl,

where m is an integer from 0 to 4, n is an integer from 1 to 4

Q represents hydroxy, carboxy, cyano, nitro, -NR6R7, -CONR6R7or-SO2NR6R7,

Z1 represents-O-, -CO-, -C(OH)R8-, -C(=N-OR8)-, -S-, -SO-, -SO2-, -N(COR8)-, -N(CO2R9)-, -N(SO2R9)-, -CO-O-, -O-CO-, -CO-NR8-, -NR8-CO-, -NR8-CO2-, -NR8-CO-NH-, -NR8-SO2- or-NR8-C(=NH)-NH-,

Z2 represents-O-, -CO-, -C(OH)R8-, -C(=N-OR8)-, -S-, -SO-, -SO2-, -NR8-, -N(COR8)-, -N(CO2R9)-, -N(SO2R9)-, -CO-O-, -O-CO-, -CO-NR8-, -NR8-CO-, -NR8-CO2-, -NR8-CO-NH-, -NR8-C(=NH)-NH-, -NR8-SO2- or-SO2-NR8-,

(CH2)mand (CH2)noptionally substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4of alkyl and hydroxy, and when m or n is not less than 2, a subset-CH2CH2groups (CH2)mand (CH2)noptionally replaced by-CH=CH-,

R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, or R6and R7related to education, together with the nitrogen atom, 3-8-membered saturated or unsaturated aliphatic heterocyclic group,

R8represents a hydrogen atom or a C1-4alkyl group, and

R9represents a C1-4alkyl group, or

(ii) karbamoilnuyu group, optionally containing 1 or 2 C1-8alkyl group optionally substituted by substituent(s)selected(s) from the group T substituents,

where carnemolla group contains two deputies and they optionally form, together with the adjacent nitrogen atom, a 3-8-membered saturated or unsaturated aliphatic heterocyclic group, optionally substituted by substituent(s)selected(s) from the group T substituents,

[39] the compound according to above item [17], where

Bcrepresents a benzene ring, optionally substituted by 1-4 substituents selected from halogen and optionally halogenated C1-4of alkyl;

Ccis a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom (for example, pyridyl, pyrimidinyl, 4-piperidyl), which is optionally substituted by 1-5 substituents selected from the

(i) halogen,

(ii) C1-4of alkyl,

(iii) C1-4alkylcarboxylic,

(iv) optionally halogenated C1-4alkoxycarbonyl,

(v C 3-8cycloalkylcarbonyl and

(vi) carbamoyl group, optionally substituted by substituent(s)selected(s)

(a) optionally halogenated C1-8of alkyl,

(b) C3-8cycloalkyl and

(c) C6-18aryl, optionally substituted by substituent(s)selected(s) halogen, C1-4the alkyl and C1-4alkyloxy;

R1crepresents a

(i) a hydrogen atom,

(ii) C2-4alkenylphenol group, optionally substituted hydroxy, or

(iii) 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom;

R2crepresents a

(i) C1-4alkyl group optionally substituted by substituent(s)selected(s)

(a) halogen,

(b) hydroxy,

(c) C1-4alkyloxy,

(d) carboxy,

(e) C1-4alkoxycarbonyl,

(f) -O-(CH2)n-OH,

(g) -O-(CH2)n-O-C1-4of alkyl,

(h) -CO-NR8-(CH2)n-OH, and

(i) -NR8-CO-(CH2)n-SO2-C1-4of alkyl,

where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group, or

(ii) C6-18aryl-C1-4alkyl group, optionally substituted C1-4the alkyl, optionally containing hydroxy;

R3crepresents a hydrogen atom or a C1-6 alkyl group; or

R2cand R3cnot necessarily related to the formation of C2-4alkylene,

[40] the compound according to above item [17], where

Bcrepresents a benzene ring, optionally substituted by 1-4 substituents selected from halogen and C1-4of alkyl;

Ccis a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, which optionally is substituted by 1-5 substituents selected from the

(i) C1-4of alkyl,

(ii) C1-4alkylcarboxylic,

(iii) optionally halogenated C1-4alkoxycarbonyl,

(iv) C3-8cycloalkylcarbonyl and

(v) carbamoyl group, optionally substituted by substituent(s)selected(s)

(a) optionally halogenated C1-8of alkyl,

(b) C3-8cycloalkyl and

(c) C6-18aryl, optionally substituted with halogen;

R1crepresents a hydrogen atom;

R2crepresents a C1-4alkyl group optionally substituted by substituent(s)selected(s)

(a) hydroxy,

(b) C1-4alkyloxy,

(c) -O-(CH2)n-OH,

(d) -O-(CH2)n-O-C1-4the alkyl and

(e) -NR8-CO-(CH2)n-SO2-C1-4of alkyl,

where n is an integer from 1 to 4 and R8PR is dstanley a hydrogen atom or a C 1-4alkyl group;

R3crepresents a hydrogen atom or a C1-6alkyl group,

[41] the compound according to above item [40], where

R2crepresents a C1-4alkyl group optionally substituted by substituent(s)selected(s)

(a) -O-(CH2)n-OH, and

(b) -O-(CH2)n-O-C1-4of alkyl,

where n is an integer from 1 to 4

[42] the compound according to above item [18], where

Bdrepresents a benzene ring, optionally substituted with halogen;

Cdis a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom;

R1drepresents a hydrogen atom;

R2drepresents a

(i) C1-4alkyl, optionally substituted by substituent(s)selected(s)

(a) C1-4alkyloxy,

(b) -O-(CH2)n-OH, and

(c) -NR8-CO-(CH2)n-SO2-C1-4of alkyl,

where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group, or

(ii) 5-8-membered heterocycle-C1-4alkyl group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, which is optionally substituted by substituent(s)selected(s)

(a) carboxy, and

(b) C alkoxycarbonyl;

R3drepresents a hydrogen atom or a C1-6alkyl group; and

Zdrepresents a C1-3alkylenes group,

[43] the compound according to above item [18], where

Bdrepresents a benzene ring, optionally substituted with halogen;

Cdis a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom;

R1drepresents a hydrogen atom;

R2drepresents a C1-4alkyl group, optionally substituted C1-4alkyloxy;

R3drepresents a hydrogen atom or a C1-6alkyl group; and

Zdrepresents a methylene group,

[44] the compound according to above item [19], where

R2erepresents (i) C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, C1-8alkylcarboxylic group, C1-8alkylsulfonyl group, C3-8cycloalkyl group, C6-18aryl group, a C6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, C6-18arylsulfonyl group, heterocyclic group, a heterocycle-C1-4alkyl group, getprocessmemoryinfo gr is polyurethane foam or a heterocycle-C 1-4alkylcarboxylic group, each of which is optionally substituted by 1-5 substituents selected from group (group T substituents), consisting of

(a) halogen,

(b) oxo,

(c) optionally halogenated C1-4of alkyl,

(d) -(CH2)m-Q,

(e) -(CH2)m-Z1-(optionally halogenated C1-4the alkyl),

(f) -(CH2)m-Z1-C3-8cycloalkyl,

(g) -(CH2)m-Z2-(CH2)n-Q,

(h) -(CH2)m-Z2-(CH2)n-Z1-(optionally halogenated C1-4the alkyl),

(i) -(CH2)m-Z2-(CH2)n-Z1-C3-8cycloalkyl,

(j) -(CH2)m-Z1-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom),

(k) -(CH2)m-Z2-C1-4alkoxy and

(l) -(CH2)m-Z2-(CH2)n-Z1-(CH2)n-Z1-C1-4of alkyl,

where m is an integer from 0 to 4, n is an integer from 1 to 4

Q represents hydroxy, carboxy, cyano, nitro, -NR6R7, -CONR6R7or-SO2NR6R7,

Z1 represents-O-, -CO-, -C(OH)R8-, -C(=N-OR8)-, -S-, -SO-, -SO2-, -N(COR8)-, -N(CO2R9)-, -N(SO2R9)-, -CO-O-, -O-CO-, -CO-NR8-, -NR8-CO-, -NR8-CO2-, -NR8-CO-NH-, -NR8-SO2- or-NR8-C(=NH)-NH-,

Z2 represents-O-, -CO-, -C(OH)R8-, -C(=N-OR8)-, -S-, -SO-, -SO2-, -NR8-, -N(COR8)-, -N(CO2R9)-, -N(SO2R9)-, -CO-O-, -O-CO-, -CO-NR8-, -NR8-CO-, -NR8-CO2-, -NR8-CO-NH-, -NR8-C(=NH)-NH-, -NR8-SO2- or-SO2-NR8-,

(CH2)mand (CH2)noptionally substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4of alkyl and hydroxy, and when m or n is not less than 2, a subset-CH2CH2groups (CH2)mand (CH2)noptionally replaced by-CH=CH-,

R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, or R6and R7related to education, together with the nitrogen atom, a 3-8-membered saturated or unsaturated aliphatic heterocyclic group,

R8represents a hydrogen atom or a C1-4alkyl group, and

R9represents a C1-4alkyl group, or

(ii) karbamoilnuyu group, optionally containing 1 or 2 C1-8 alkyl group optionally substituted by substituent(s)selected(s) from the group T substituents,

where carnemolla group contains two deputies and they optionally form, together with the adjacent nitrogen atom, a 3-8-membered saturated or unsaturated aliphatic heterocyclic group, optionally substituted by substituent(s)selected(s) from the group T substituents,

[45] the compound according to above item [19], where

Berepresents a benzene ring, optionally substituted with halogen;

Cerepresents a phenyl group optionally substituted by optionally halogenated C1-4by alkyl;

R2erepresents a C1-4alkyl group, optionally substituted-O-(CH2)n-OH, where n is an integer from 1 to 4

[46] the compound according to above item [19], where

Berepresents a benzene ring, optionally substituted with halogen;

Cerepresents a phenyl group optionally substituted by optionally halogenated C1-4by alkyl;

R2erepresents a C1-4alkyl group, substituted-O-(CH2)n-OH, where n is an integer from 1 to 4

[47] the compound according to above item [20], where

R2frepresents (i) C1-8alkyl group, a C alkenylphenol group, C2-8alkylamino group, C1-8alkylcarboxylic group, C1-8alkylsulfonyl group, C3-8cycloalkyl group, C6-18aryl group, a C6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, C6-18arylsulfonyl group, heterocyclic group, a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted by 1-5 substituents selected from group (group T substituents), consisting of

(a) halogen,

(b) oxo,

(c) optionally halogenated C1-4of alkyl,

(d) -(CH2)m-Q,

(e) -(CH2)m-Z1-(optionally halogenated C1-4the alkyl),

(f) -(CH2)m-Z1-C3-8cycloalkyl,

(g) -(CH2)m-Z2-(CH2)n-Q,

(h) -(CH2)m-Z2-(CH2)n-Z1-(optionally halogenated C1-4the alkyl),

(i) -(CH2)m-Z2-(CH2)n-Z1-C3-8cycloalkyl,

(j) -(CH2)m-Z1-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic gr the PPU, containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom),

(k) -(CH2)m-Z2-C1-4alkoxy and

(l) -(CH2)m-Z2-(CH2)n-Z1-(CH2)n-Z1-C1-4of alkyl,

where m is an integer from 0 to 4, n is an integer from 1 to 4

Q represents hydroxy, carboxy, cyano, nitro, -NR6R7, -CONR6R7or-SO2NR6R7,

Z1 represents-O-, -CO-, -C(OH)R8-, -C(=N-OR8)-, -S-, -SO-, -SO2-, -N(COR8)-, -N(CO2R9)-, -N(SO2R9)-, -CO-O-, -O-CO-, -CO-NR8-, -NR8-CO-, -NR8-CO2-, -NR8-CO-NH-, -NR8-SO2- or-NR8-C(=NH)-NH-,

Z2 represents-O-, -CO-, -C(OH)R8-, -C(=N-OR8)-, -S-, -SO-, -SO2-, -NR8-, -N(COR8)-, -N(CO2R9)-, -N(SO2R9)-, -CO-O-, -O-CO-, -CO-NR8-, -NR8-CO-, -NR8-CO2-, -NR8-CO-NH-, -NR8-C(=NH)-NH-, -NR8-SO2- or-SO2-NR8-,

(CH2)mand (CH2)noptionally substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4of alkyl and hydroxy, and when m or n is not less than 2, a subset-CH2CH2groups (CH2)mand (CH2)noptionally replaced by-CH=CH-,

R6and R7are about incopyme or different and each represents a hydrogen atom or a C 1-4alkyl group, or R6and R7related to education, together with the nitrogen atom, a 3-8-membered saturated or unsaturated aliphatic heterocyclic group,

R8represents a hydrogen atom or a C1-4alkyl group, and

R9represents a C1-4alkyl group, or

(ii) karbamoilnuyu group, optionally containing 1 or 2 C1-8alkyl group optionally substituted by substituent(s)selected(s) from the group T substituents,

where carnemolla group contains two deputies and they optionally form, together with the adjacent nitrogen atom, a 3-8-membered saturated or unsaturated aliphatic heterocyclic group, optionally substituted by substituent(s)selected(s) from the group T substituents,

[48] the compound according to above item [20], where

Bfrepresents a benzene ring, optionally substituted with halogen;

Cfrepresents a phenyl group, optionally substituted with halogen;

R2frepresents a

(i) C1-4alkyl group, optionally substituted by 1-5 substituents selected from the group consisting of

(a) hydroxy,

(b) -O-(CH2)n-OH,

(c) -NR8-(CH2)n-O-C1-4of alkyl,

(d) -NR8-(CH2)n-heterocyclic group (decree is owned by the heterocyclic group preferably is a 5-8-membered heterocyclic group, containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom), and

(e) -NR8-(CH2)n-SO2-C1-4of alkyl,

where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group,

(ii) C6-18aryl group, optionally substituted by 1-5 substituents selected from the group consisting of

(a) C1-4the alkyl, optionally substituted by substituent(s)selected(s) hydroxy, -NR8-(CH2)n-OH, -NR8-(CH2)n-O-C1-4of alkyl, -NR8-(CH2)n-heterocyclic group (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom) and-NR8-(CH2)n-SO2-C1-4of alkyl, and

(b) -CO-NR8-(CH2)n-O-C1-4of alkyl,

where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group, or

(iii) C6-18aryl-C1-4alkyl group, optionally substituted by 1-5 substituents selected from the group consisting of

(a) carboxy,

(b) C1-4alkoxycarbonyl and

(c) -CO-NR8-(CH2)n-O-C1-4of alkyl,

where n is an integer from 1 to 4 and R8is sobo is a hydrogen atom or a C 1-4alkyl group;

R3frepresents a hydrogen atom or a C1-6alkyl group; or

R2fand R3fnot necessarily related to the formation of C2-4alkylene; and

Zfrepresents a C1-3alkylenes group,

[49] the compound according to above item [20], where

Bfrepresents a benzene ring, optionally substituted with halogen;

Cfrepresents a phenyl group, optionally substituted with halogen;

R2frepresents a C1-4alkyl group, optionally substituted by 1-5 substituents selected from the group consisting of

(a) hydroxy, and

(b) -O-(CH2)n-OH, where n is an integer from 1 to 4;

R3frepresents a hydrogen atom or a C1-6alkyl group; and

Zfrepresents a methylene,

[50] the compound according to above item [49], where

R2frepresents a C1-4alkyl group, substituted-O-(CH2)n-OH, where n is an integer from 1 to 4

[51] the compound according to above item [21], where

R2grepresents (i) C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, C1-8alkylcarboxylic group, C1-8alkylsulfonyl group, C3-8cycloalkyl group, C6-18aryl group 6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, C6-18arylsulfonyl group, heterocyclic group, a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted by 1-5 substituents selected from group (group T substituents), consisting of

(a) halogen,

(b) oxo,

(c) optionally halogenated C1-4of alkyl,

(d) -(CH2)m-Q,

(e) -(CH2)m-Z1-(optionally halogenated C1-4the alkyl),

(f) -(CH2)m-Z1-C3-8cycloalkyl,

(g) -(CH2)m-Z2-(CH2)n-Q,

(h) -(CH2)m-Z2-(CH2)n-Z1-(optionally halogenated C1-4the alkyl),

(i) -(CH2)m-Z2-(CH2)n-Z1-C3-8cycloalkyl,

(j) -(CH2)m-Z1-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom),

(k) -(CH2)m-Z2-C1-4alkoxy and

(l) -(CH2) m-Z2-(CH2)n-Z1-(CH2)n-Z1-C1-4of alkyl,

where m is an integer from 0 to 4, n is an integer from 1 to 4

Q represents hydroxy, carboxy, cyano, nitro, -NR6R7, -CONR6R7or-SO2NR6R7,

Z1 represents-O-, -CO-, -C(OH)R8-, -C(=N-OR8)-, -S-, -SO-, -SO2-, -N(COR8)-, -N(CO2R9)-, -N(SO2R9)-, -CO-O-, -O-CO-, -CO-NR8-, -NR8-CO-, -NR8-CO2-, -NR8-CO-NH-, -NR8-SO2- or-NR8-C(=NH)-NH-,

Z2 represents-O-, -CO-, -C(OH)R8-, -C(=N-OR8)-, -S-, -SO-, -SO2-, -NR8-, -N(COR8)-, -N(CO2R9)-, -N(SO2R9)-, -CO-O-, -O-CO-, -CO-NR8-, -NR8-CO-, -NR8-CO2-, -NR8-CO-NH-, -NR8-C(=NH)-NH-, -NR8-SO2- or-SO2-NR8-,

(CH2)mand (CH2)noptionally substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4of alkyl and hydroxy, and when m or n is not less than 2, a subset-CH2CH2groups (CH2)mand (CH2)noptionally replaced by-CH=CH-,

R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, or R6and R7related to education, together with the nitrogen atom, 3-8-membered us is on or unsaturated aliphatic heterocyclic group,

R8represents a hydrogen atom or a C1-4alkyl group, and

R9represents a C1-4alkyl group, or

(ii) karbamoilnuyu group, optionally containing 1 or 2 C1-8alkyl group optionally substituted by substituent(s)selected(s) from the group T substituents,

where carnemolla group contains two deputies and they optionally form, together with the adjacent nitrogen atom, a 3-8-membered saturated or unsaturated aliphatic heterocyclic group, optionally substituted by substituent(s)selected(s) from the group T substituents,

[52] the compound according to above item [21], where

Bgrepresents a benzene ring, optionally substituted C1-4by alkyl;

Cgis a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, which is optionally substituted C1-4by alkyl;

R2grepresents a

(i) C1-4alkyl group, optionally substituted hydroxy,

(ii) C6-18aryl group optionally substituted by substituent(s)selected(s)

(a) nitro,

(b) amino,

(c) -CO-NR8-(CH2)n-O-C1-4of alkyl,

(d) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(e) -NR8-CO-(CH2)n -NR6R7,

(f) -NR8-CO-(CH2)n-COOH

(g) -NR8-CO-(CH2)n-CO2-C1-4the alkyl and

(h) -NR8-CO-(CH2)m-O-(CH2)n-O-C1-4of alkyl,

where m is an integer from 0 to 4, n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, and R8represents a hydrogen atom or a C1-4alkyl group, or

(iii) C6-18aryl-C1-4alkyl group optionally substituted by substituent(s)selected(s)

(a) carboxy,

(b) C1-4alkoxycarbonyl and

(c) -CO-NR8-(CH2)n-O-C1-4of alkyl,

where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group;

R3grepresents a hydrogen atom or a C1-6alkyl group; or

R2gand R3gnot necessarily related to the formation of C2-4alkylene,

[53] the compound according to above item [21], where

R2grepresents a

(i) C6-18aryl group optionally substituted by substituent(s)selected(s)

(a) nitro,

(b) amino,

(c) -CO-NR8-(CH2)n-O-C1-4of alkyl,

(d) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(e) -NR8-CO-(CH2)n-N 6R7,

(f) -NR8-CO-(CH2)n-COOH

(g) -NR8-CO-(CH2)n-CO2-C1-4the alkyl and

(h) -NR8-CO-(CH2)m-O-(CH2)n-O-C1-4of alkyl,

where m is an integer from 0 to 4, n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, and R8represents a hydrogen atom or a C1-4alkyl group, or

(ii) C6-18aryl-C1-4alkyl group substituted by substituent(s)selected(s)

(a) carboxy,

(b) C1-4alkoxycarbonyl and

(c) -CO-NR8-(CH2)n-O-C1-4of alkyl,

where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group,

[54] the compound according to above item [1], where

Rather it represents a C6-18aryl group substituted by substituent(s)selected(s)

(i) fenoxaprop, optionally substituted by 1-5 substituents selected from the

(a) halogen,

(b) optionally halogenated C1-4of alkyl,

(c) hydroxy-C1-4of alkyl,

(d) heterocycle-C1-4the alkyl (preferably 5-8-membered heterocycle-C1-4of alkyl, where the specified 5-8-membered heterocycle contains 1-3 heteroatoms selected from nitrogen atom, oxygen atom and obazatelno oxidized sulfur atom, such as imidazolyl, triazolyl and the like),

(e) optionally halogenated C1-4alkyloxy,

(f) C1-4alkylcarboxylic,

(g) cyano,

(h) carbamoyl, optionally substituted C1-8the alkyl, and

(i) C1-4alkoxycarbonyl,

(ii) phenyl-C1-3alkyloxy, optionally substituted by 1-5 substituents selected from the

(a) halogen,

(b) optionally halogenated C1-4of alkyl,

(c) hydroxy-C1-4of alkyl,

(d) heterocycle-C1-4the alkyl (preferably 5-8-membered heterocycle-C1-4of alkyl, where the specified 5-8-membered heterocycle contains 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, such as imidazolyl, triazolyl and the like),

(e) optionally halogenated C1-4alkyloxy,

(f) C1-4alkylcarboxylic,

(g) cyano,

(h) carbamoyl, optionally substituted C1-8the alkyl, and

(i) C1-4alkoxycarbonyl,

(iii) 5-8-membered heterozygosity containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, which optionally is substituted by 1-5 substituents selected from the

(a) halogen,

(b) optionally halogenated C1-4of alkyl,

(c) hydroxy-C1-4of alkyl,

(d) heterocycle-C1-4the alkyl (preferably 5-8-membered Goethe is Ozil-C 1-4of alkyl, where the specified 5-8-membered heterocycle contains 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, such as imidazolyl, triazolyl and the like),

(e) optionally halogenated C1-4alkyloxy,

(f) C1-4alkylcarboxylic,

(g) cyano,

(h) carbamoyl, optionally substituted C1-8the alkyl, and

(i) C1-4alkoxycarbonyl, and

(iv) 5-8-membered heterocycle-C1-3alkyloxy containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, which optionally is substituted by 1-5 substituents selected from the

(a) halogen,

(b) optionally halogenated C1-4of alkyl,

(c) hydroxy-C1-4of alkyl,

(d) heterocycle-C1-4the alkyl (preferably 5-8-membered heterocycle-C1-4of alkyl, where the specified 5-8-membered heterocycle contains 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, such as imidazolyl, triazolyl and the like),

(e) optionally halogenated C1-4alkyloxy,

(f) C1-4alkylcarboxylic,

(g) cyano,

(h) carbamoyl, optionally substituted C1-8the alkyl, and

(i) C1-4alkoxycarbonyl;

where C6-18aryl group is additionally optionally substituted by 1-4 substituents, selected the data from halogen, C1-4of alkyl, hydroxy-C1-4the alkyl and C1-4alkyloxy;

R1represents a

(i) a hydrogen atom,

(ii) a cyano or

(iii) C1-4alkyl group or a C2-4alkenylphenol group, each of which is optionally substituted by-NR8-CO-(CH2)n-NR6R7,

where n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, R8represents a hydrogen atom or a C1-4alkyl group, and when n is not less than 2, a subset-CH2CH2group (CH2)noptionally replaced by-CH=CH-;

R2represents a C1-8alkyl group, a C2-8alkenylphenol group or a C2-8alkylamino group, each of which is optionally substituted by substituent(s)selected(s)

(a) hydroxy,

(b) carboxy,

(c) cyano,

(d) optionally halogenated C1-4alkyloxy,

(e) -O-(CH2)n-OH,

(f) -O-(CH2)n-O-CO-NH2,

(g) -O-(CH2)n-O-(optionally halogenated C1-4the alkyl),

(h) -O-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(i) -O-(CH2)n-SO2-C6-18aryl,

(j) -O-(CH2)n-SO2-(CH2)n-OH,

(k) -O-(CH2 )n-NR8-CO-C1-4of alkyl,

(l) -O-(CH2)n-NR8-CO-(CH2)n-SO2-C1-4of alkyl,

(m) -O-(CH2)n-NR8-SO2-(optionally halogenated C1-4the alkyl),

(n) -CO-NR8-(CH2)n-OH,

(o) -CO-NR8-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(p) -CO-NR8-O-C1-4of alkyl,

(q) -NR6R7,

(r) -NR8-(CH2)n-OH,

(s) -NR8-(CH2)n-SO2-C1-4of alkyl,

(t) -NR8-CO-(optionally halogenated C1-4the alkyl),

(u) -NR8-CO-(CH2)n-OH,

(v) -NR8-CO-(CH2)n-CN

(w) -NR8-CO-(CH2)n-NR6R7,

(x) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(y) -NR8-CO-(CH2)n-SO-(optionally halogenated C1-4the alkyl),

(z) -NR8-CO-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(aa) -NR8-CO-(CH2)n-SO2-C3-8cycloalkyl,

(bb) -NR8-CO-(CH2)n-NR8-SO2-C1-4of alkyl,

(cc) -NR8-CO2-(CH2)n-SO2-C1-4of alkyl,

(dd) -NR8-CO-NH-(CH2)n-SO2-C1-4of alkyl,

(ee) -NR8-CO-NH-O-C1-4of alkyl,

(ff) -NR8-CO-NH-(CH2)n-O-C1-4

(gg) -NR8-C(=NH)-NH-C1-4of alkyl,

(hh) -NR8-SO2-(CH2)n-SO2-C1-4of alkyl,

(ii) -S-(CH2)n-OH,

(jj) -SO-(CH2)n-OH,

(kk) -SO2-(CH2)n-OH, and

(ll) -NR8-CO-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, which is optionally substituted by substituent(s)selected(s) hydroxy, C1-4the alkyl, optionally oxidized C1-4alkylthio, -CO-C1-4of alkyl, -CO-O-C1-4of alkyl, -CO-NH-C1-4of alkyl, -CONH2, -SO2-C1-4of alkyl, -SO2-NH-C1-4of alkyl, -SO2NH2and the like),

where n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, R8represents a hydrogen atom or a C1-4alkyl group, a group (CH2)noptionally substituted halogenated C1-4the alkyl or hydroxy, and when n is not less than 2, a subset-CH2CH2group (CH2)noptionally replaced by-CH=CH-;

R3represents a hydrogen atom or a C1-6and kilou group; or

R1and R2not necessarily related to educationor; or

R2and R3not necessarily related to the formation of C2-4alkylene, optionally substituted aminogroups.

Particularly preferably, R2represents a C1-8alkyl group, a C2-8alkenylphenol group or a C2-8alkylamino group (in particular, C1-8alkyl group), each of which is optionally substituted by substituent(s)selected(s)

(a) hydroxy,

(b) carboxy,

(c) cyano,

(d) optionally halogenated C1-4alkyloxy,

(e) -O-(CH2)n-OH (where the group (CH2)noptionally substituted by hydroxy),

(f) -O-(CH2)n-O-CO-NH2,

(g) -O-(CH2)n-O-(optionally halogenated C1-4the alkyl),

(h) -O-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(i) -O-(CH2)n-SO2-C6-18aryl,

(j) -O-(CH2)n-SO2-(CH2)n-OH,

(k) -O-(CH2)n-NR8-CO-C1-4of alkyl,

(l) -O-(CH2)n-NR8-CO-(CH2)n-SO2-C1-4of alkyl,

(m) -O-(CH2)n-NR8-SO2-(optionally halogenated C1-4the alkyl),

(n) -CO-NR8-(CH2)n-OH,

(o) -CO-NR8/sup> -(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(p) -CO-NR8-O-C1-4of alkyl,

(q) -NR6R7,

(r) -NR8-(CH2)n-OH,

(s) -NR8-(CH2)n-SO2-C1-4of alkyl,

(t) -NR8-CO-(optionally halogenated C1-4the alkyl),

(u) -NR8-CO-(CH2)n-OH (where the group (CH2)noptionally substituted by optionally halogenated C1-4the alkyl or hydroxy),

(v) -NR8-CO-(CH2)n-CN

(w) -NR8-CO-(CH2)n-NR6R7(when n is not less than 2, a subset-CH2CH2group (CH2)noptionally replaced by-CH=CH-),

(x) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(y) -NR8-CO-(CH2)n-SO-(optionally halogenated C1-4the alkyl),

(z) -NR8-CO-(CH2)n-SO2-(optionally halogenated C1-4the alkyl) (where the group (CH2)noptionally substituted C1-4by alkyl),

(aa) -NR8-CO-(CH2)n-SO2-C3-8cycloalkyl,

(bb) -NR8-CO-(CH2)n-NR8-SO2-C1-4of alkyl,

(cc) -NR8-CO2-(CH2)n-SO2-C1-4of alkyl,

(dd) -NR8-CO-NH-(CH2)n-SO2-C1-4of alkyl,

(ee) -NR8-CO-NH-O-C1-4of alkyl,

(ff) -NR8-C-NH-(CH 2)n-O-C1-4of alkyl,

(gg) -NR8-C(=NH)-NH-C1-4of alkyl,

(hh) -NR8-SO2-(CH2)n-SO2-C1-4of alkyl,

(ii) -S-(CH2)n-OH,

(jj) -SO-(CH2)n-OH,

(kk) -SO2-(CH2)n-OH, and

(ll) -NR8-CO-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, which is optionally substituted by substituent(s)selected(s) hydroxy, C1-4the alkyl, optionally oxidized C1-4alkylthio, -CO-C1-4of alkyl, -CO-O-C1-4of alkyl, -CO-NH-C1-4of alkyl, -CONH2, -SO2-C1-4of alkyl, -SO2-NH-C1-4of alkyl, -SO2NH2and the like),

where n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, and R8represents a hydrogen atom or a C1-4alkyl group,

[55] the compound according to above item [1], where

A represents a C6-18aryl group substituted by substituent(s)selected(s)

(i) fenoxaprop, substituted by 1-5 substituents selected from the

(a) halogen,

(b) optionally halogenated C 1-4of alkyl,

(c) hydroxy-C1-4of alkyl,

(d) heterocycle-C1-4the alkyl (preferably 5-8-membered heterocycle-C1-4of alkyl, where the specified 5-8-membered heterocycle contains 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, such as imidazolyl and the like),

(e) optionally halogenated C1-4alkyloxy,

(f) cyano,

(g) carbamoyl, optionally substituted C1-8the alkyl, and

(h) C1-4alkoxycarbonyl,

(ii) phenyl-C1-3alkyloxy, substituted by 1-5 substituents selected from the

(a) halogen,

(b) optionally halogenated C1-4of alkyl,

(c) hydroxy-C1-4of alkyl,

(d) heterocycle-C1-4the alkyl (preferably 5-8-membered heterocycle-C1-4of alkyl, where the specified 5-8-membered heterocycle contains 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, such as imidazolyl and the like),

(e) optionally halogenated C1-4alkyloxy,

(f) cyano,

(g) carbamoyl, optionally substituted C1-8of alkyl, and

(h) C1-4alkoxycarbonyl,

(iii) 5-8-membered heterozygosity containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, which optionally is substituted by 1-5 substituents selected is from

(a) halogen,

(b) optionally halogenated C1-4of alkyl,

(c) hydroxy-C1-4of alkyl,

(d) heterocycle-C1-4the alkyl (preferably 5-8-membered heterocycle-C1-4of alkyl, where the specified 5-8-membered heterocycle contains 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, such as imidazolyl and the like),

(e) optionally halogenated C1-4alkyloxy,

(f) cyano,

(g) carbamoyl, optionally substituted C1-8of alkyl, and

(h) C1-4alkoxycarbonyl and

(iv) 5-8-membered heterocycle-C1-3alkyloxy containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, which is substituted by 1-5 substituents selected from the

(a) halogen,

(b) optionally halogenated C1-4of alkyl,

(c) hydroxy-C1-4of alkyl,

(d) heterocycle-C1-4the alkyl (preferably 5-8-membered heterocycle-C1-4of alkyl, where the specified 5-8-membered heterocycle contains 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, such as imidazolyl and the like),

(e) optionally halogenated C1-4alkyloxy,

(f) cyano,

(g) carbamoyl, optionally substituted C1-8the alkyl, and

(h) C1-4alkoxycarbonyl;

where C6-18arilin the group is additionally optionally substituted by 1-4 substituents, selected from halogen and optionally halogenated C1-4of alkyl;

R1represents a hydrogen atom;

R2represents a C1-8alkyl group, a C2-8alkenylphenol group or a C2-8alkylamino group, each of which is substituted by substituent(s)selected(s)

(a) hydroxy,

(b) optionally halogenated C1-4alkyloxy,

(c) -O-(CH2)n-OH,

(d) -O-(CH2)n-O-CO-NH2,

(e) -O-(CH2)n-O-C1-4of alkyl,

(f) -O-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(g) -O-(CH2)n-SO2-C6-18aryl,

(h) -O-(CH2)n-SO2-(CH2)n-OH,

(i) -O-(CH2)n-NR8-SO2-(optionally halogenated C1-4the alkyl),

(j) -CO-NR8-(CH2)n-OH,

(k) -CO-NR8-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(l) -NR6R7,

(m) -NR8-(CH2)n-OH,

(n) -NR8-(CH2)n-SO2-C1-4of alkyl,

(o) -NR8-CO-(CH2)n-OH,

(p) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(q) -NR8-CO-(CH2)n-SO-(optionally halogenated C1-4the alkyl),

(r) -NR8-CO-(CH2)n-SO2-(optionally halogenated C14 the alkyl),

(s) -NR8-CO-(CH2)n-SO2-C3-8cycloalkyl,

(t) -NR8-CO2-(CH2)n-SO2-C1-4of alkyl,

(u) -NR8-CO-NH-(CH2)n-SO2-C1-4of alkyl,

(v) -NR8-SO2-(CH2)n-SO2-C1-4of alkyl,

(w) -S-(CH2)n-OH,

(x) -SO-(CH2)n-OH,

(y) -SO2-(CH2)n-OH, and

(z) -NR8-CO-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, which is optionally substituted by substituent(s)selected(s) hydroxy, C1-4the alkyl, optionally oxidized C1-4alkylthio, -CO-C1-4of alkyl, -CO-NH-C1-4of alkyl, -CONH2, -SO2-C1-4of alkyl, -SO2-NH-C1-4of alkyl, -SO2NH2and the like),

where n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, R8represents a hydrogen atom or a C1-4alkyl group and the group (CH2)noptionally substituted C1-4the alkyl or hydroxy);

R3is an atom of water is kind or C 1-6alkyl group; or

R1and R2not necessarily related to educationor; or

R2and R3not necessarily related to the formation of C2-4alkylene,

particularly preferably, R2represents a C1-8alkyl group, a C2-8alkenylphenol group or a C2-8alkylamino group (in particular, C1-8alkyl group), each of which is substituted by substituent(s)selected(s)

(a) hydroxy,

(b) optionally halogenated C1-4alkyloxy,

(c) -O-(CH2)n-OH (where the group (CH2)noptionally substituted by hydroxy),

(d) -O-(CH2)n-O-CO-NH2,

(e) -O-(CH2)n-O-C1-4of alkyl,

(f) -O-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(g) -O-(CH2)n-SO2-C6-18aryl,

(h) -O-(CH2)n-SO2-(CH2)n-OH,

(i) -O-(CH2)n-NR8-SO2-(optionally halogenated C1-4the alkyl),

(j) -CO-NR8-(CH2)n-OH,

(k) -CO-NR8-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(l) -NR6R7,

(m) -NR8-(CH2)n-OH,

(n) -NR8-(CH2)n-SO2-C1-4of alkyl,

(o) -NR8-CO-(CH2) n-OH (where the group (CH2)noptionally substituted C1-4by alkyl),

(p) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(q) -NR8-CO-(CH2)n-SO-(optionally halogenated C1-4the alkyl),

(r) -NR8-CO-(CH2)n-SO2-(optionally halogenated C1-4the alkyl) (where the group (CH2)noptionally substituted C1-4by alkyl),

(s) -NR8-CO-(CH2)n-SO2-C3-8cycloalkyl,

(t) -NR8-CO2-(CH2)n-SO2-C1-4of alkyl,

(u) -NR8-CO-NH-(CH2)n-SO2-C1-4of alkyl,

(v) -NR8-SO2-(CH2)n-SO2-C1-4of alkyl,

(w) -S-(CH2)n-OH,

(x) -SO-(CH2)n-OH,

(y) -SO2-(CH2)n-OH, and

(z) -NR8-CO-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, which is optionally substituted by substituent(s)selected(s) hydroxy, C1-4the alkyl, optionally oxidized C1-4alkylthio, -CO-C1-4of alkyl, -CO-NH-C1-4of alkyl, -CONH2, -SO2-C1-4of alkyl, -SO2-NH-C1-4of alkyl, -SO2NH2 and the like),

where n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, and R8represents a hydrogen atom or a C1-4alkyl group,

[56] the compound according to above item [55], where

R2represents a

(i) C5-8alkyl group, a substituted hydroxy,

(ii) C1-8alkyl group substituted by substituent(s)selected(s)

(a) halogenated C1-4alkyloxy,

(b) -O-(CH2)n-OH,

(c) -O-(CH2)n-O-CO-NH2,

(d) -O-(CH2)n-O-(optionally halogenated C1-4the alkyl),

(e) -O-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(f) -O-(CH2)n-SO2-C6-18aryl,

(g) -O-(CH2)n-NR8-SO2-(optionally halogenated C1-4the alkyl),

(h) -CO-NR8-(CH2)n-OH,

(i) -CO-NR8-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(j) -NR8-(CH2)n-SO2-C1-4of alkyl,

(k) -NR8-CO-(CH2)n-OH,

(l) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(m) -NR8-CO-(CH2)n-SO-(optionally halogenated C1-4the alkyl),

(n) -NR8-CO-(CH2 )n-SO2-(optionally halogenated C1-4the alkyl),

(o) -NR8-CO-(CH2)n-SO2-C3-8cycloalkyl,

(p) -NR8-CO2-(CH2)n-SO2-C1-4of alkyl,

(q) -NR8-CO-NH-(CH2)n-SO2-C1-4of alkyl,

(r) -NR8-SO2-(CH2)n-SO2-C1-4of alkyl,

(s) -S-(CH2)n-OH,

(t) -SO-(CH2)n-OH,

(u) -SO2-(CH2)n-OH, and

(v) -NR8-CO-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, which is optionally substituted by substituent(s)selected(s) hydroxy, C1-4the alkyl, optionally oxidized C1-4alkylthio, -CO-C1-4of alkyl, -CO-NH-C1-4of alkyl, -CONH2, -SO2-C1-4of alkyl, -SO2-NH-C1-4of alkyl, -SO2NH2and the like),

where n is an integer from 1 to 4, R8represents a hydrogen atom or a C1-4alkyl group and the group (CH2)noptionally substituted C1-4the alkyl,

(iii) C2-8alkenylphenol group, optionally substituted hydroxy, or

(iv) C2-8alkylamino group, long is correctly substituted hydroxy,

particularly preferably, R2represents a

(i) C5-8alkyl group, a substituted hydroxy,

(ii) C1-8alkyl group substituted by substituent(s)selected(s)

(a) halogenated C1-4alkyloxy,

(b) -O-(CH2)n-OH (where the group (CH2)noptionally substituted by hydroxy),

(c) -O-(CH2)n-O-CO-NH2,

(d) -O-(CH2)n-O-(optionally halogenated C1-4the alkyl),

(e) -O-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(f) -O-(CH2)n-SO2-C6-18aryl,

(g) -O-(CH2)n-NR8-SO2-(optionally halogenated C1-4the alkyl),

(h) -CO-NR8-(CH2)n-OH,

(i) -CO-NR8-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(j) -NR8-(CH2)n-SO2-C1-4of alkyl,

(k) -NR8-CO-(CH2)n-OH (where the group (CH2)noptionally substituted C1-4by alkyl),

(l) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(m) -NR8-CO-(CH2)n-SO-(optionally halogenated C1-4the alkyl),

(n) -NR8-CO-(CH2)n-SO2-(optionally halogenated C1-4the alkyl) (where the group (CH2)noptionally substituted C1-4by alkyl),

(o) -NR 8-CO-(CH2)n-SO2-C3-8cycloalkyl,

(p) -NR8-CO2-(CH2)n-SO2-C1-4of alkyl,

(q) -NR8-CO-NH-(CH2)n-SO2-C1-4of alkyl,

(r) -NR8-SO2-(CH2)n-SO2-C1-4of alkyl,

(s) -S-(CH2)n-OH,

(t) -SO-(CH2)n-OH,

(u) -SO2-(CH2)n-OH, and

(v) -NR8-CO-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, which is optionally substituted by substituent(s)selected(s) hydroxy, C1-4the alkyl, optionally oxidized C1-4alkylthio, -CO-C1-4of alkyl, -CO-NH-C1-4of alkyl, -CONH2, -SO2-C1-4of alkyl, -SO2-NH-C1-4of alkyl, -SO2NH2and the like),

where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group,

(iii) C2-8alkenylphenol group, optionally substituted hydroxy, or

(iv) C2-8alkylamino group, optionally substituted hydroxy,

[57] the compound according to above item [1], which is selected from the following (A)to(H):

(A) compound (I), where

W made the focus of a CR 1;

A represents phenyloxy-C6-18aryl group, where phenyloxy-part optionally substituted by 1-5 substituents selected from the

(i) halogen,

(ii) optionally halogenated C1-4of alkyl,

(iii) hydroxy-C1-4of alkyl,

(iv) heterocycle-C1-4the alkyl (preferably 5-8-membered heterocycle-C1-4of alkyl, where the specified 5-8-membered heterocycle contains 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, such as imidazolyl, triazolyl and the like),

(v) optionally halogenated C1-4alkyloxy,

(vi) C1-4alkylcarboxylic,

(vii) cyano,

(viii) carbamoyl, optionally substituted C1-8the alkyl, and

(ix) C1-4alkoxycarbonyl, and

C6-18the aryl part is optionally substituted by 1-4 substituents selected from halogen, C1-4of alkyl, hydroxy-C1-4of alkyl, C1-4alkyloxy, carboxy and C1-4alkoxycarbonyl;

X1 represents-NR3'-where R3'represents a hydrogen atom or a C1-6alkyl group;

R1represents a

(i) a hydrogen atom,

(ii) a cyano or

(iii) C1-4alkyl group or a C2-4alkenylphenol group, each of which is optionally substituted by-NR8-CO-(CH2)n-NR6R7where n Rawa is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, R8represents a hydrogen atom or a C1-4alkyl group, and when n is not less than 2, a subset-CH2CH2groups (CH2)noptionally replaced by-CH=CH-; and

R2represents (i) hydrogen atom or (ii) C1-8alkyl group, a C2-8alkenylphenol group or a C2-8alkylamino group, each of which is optionally substituted by substituent(s)selected(s)

(a) hydroxy,

(b) carboxy,

(c) cyano,

(d) optionally halogenated C1-4alkyloxy,

(e) -O-(CH2)n-OH,

(f) -O-(CH2)n-O-CO-NH2,

(g) -O-(CH2)n-O-(optionally halogenated C1-4the alkyl),

(h) -O-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(i) -O-(CH2)n-SO2-C6-18aryl,

(j) -O-(CH2)n-SO2-(CH2)n-OH,

(k) -O-(CH2)n-NR8-CO-C1-4of alkyl,

(l) -O-(CH2)n-NR8-CO-(CH2)n-SO2-C1-4of alkyl,

(m) -O-(CH2)n-NR8-SO2-(optionally halogenated C1-4the alkyl),

(n) -CO-NR8-(CH2)n-OH,

(o) -CO-NR8-(CH2)n-SO2-(long what) halogenated C 1-4the alkyl),

(p) -CO-NR8-O-C1-4of alkyl,

(q) -NR6R7,

(r) -NR8-(CH2)n-OH,

(s) -NR8-(CH2)n-SO2-C1-4of alkyl,

(t) -NR8-CO-(optionally halogenated C1-4the alkyl),

(u) -NR8-CO-(CH2)n-OH,

(v) -NR8-CO-(CH2)n-CN

(w) -NR8-CO-(CH2)n-NR6R7,

(x) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(y) -NR8-CO-(CH2)n-SO-(optionally halogenated C1-4the alkyl),

(z) -NR8-CO-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(aa) -NR8-CO-(CH2)n-SO2-C3-8cycloalkyl,

(bb) -NR8-CO-(CH2)n-NR8-SO2-C1-4of alkyl,

(cc) -NR8-CO2-(CH2)n-SO2-C1-4of alkyl,

(dd) -NR8-CO-NH-(CH2)n-SO2-C1-4of alkyl,

(ee) -NR8-CO-NH-O-C1-4of alkyl,

(ff) -NR8-CO-NH-(CH2)n-O-C1-4of alkyl,

(gg) -NR8-C(=NH)-NH-C1-4of alkyl,

(hh) -NR8-SO2-(CH2)n-SO2-C1-4of alkyl,

(ii) -S-(CH2)n-OH,

(jj) -SO-(CH2)n-OH,

(kk) -SO2-(CH2)n-OH, and

(ll) -NR8-CO-(optionally substituted heterocyclic group) (this heterocyclic group prefer is Ino is a 5-8-membered heterocyclic group, containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, which is optionally substituted by substituent(s)selected(s) hydroxy, C1-4the alkyl, optionally oxidized C1-4alkylthio, -CO-C1-4of alkyl, -CO-O-C1-4of alkyl, -CO-NH-C1-4of alkyl, -CONH2, -SO2-C1-4of alkyl, -SO2-NH-C1-4of alkyl, -SO2NH2and the like),

where n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, R8represents a hydrogen atom or a C1-4alkyl group, a group (CH2)noptionally substituted by optionally halogenated C1-4the alkyl or hydroxy, and when n is not less than 2, a subset-CH2CH2groups (CH2)noptionally replaced by-CH=CH-; or

R1and R2not necessarily related to education; or

R2and R3'not necessarily related to the formation of C2-4alkylene, optionally substituted aminogroups,

R2aespecially preferably represents C1-8alkyl group, a C2-8alkenylphenol group or a C2-8alkylamino group (in particular, C1-8alkyl group), each of which is optional is entrusted substituted by substituent(s), the selected(s)

(a) hydroxy,

(b) carboxy,

(c) cyano,

(d) optionally halogenated C1-4alkyloxy,

(e) -O-(CH2)n-OH (where the group (CH2)noptionally substituted by hydroxy),

(f) -O-(CH2)n-O-CO-NH2,

(g) -O-(CH2)n-O-(optionally halogenated C1-4the alkyl),

(h) -O-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(i) -O-(CH2)n-SO2-C6-18aryl,

(j) -O-(CH2)n-SO2-(CH2)n-OH,

(k) -O-(CH2)n-NR8-CO-C1-4of alkyl,

(l) -O-(CH2)n-NR8-CO-(CH2)n-SO2-C1-4of alkyl,

(m) -O-(CH2)n-NR8-SO2-(optionally halogenated C1-4the alkyl),

(n) -CO-NR8-(CH2)n-OH,

(o) -CO-NR8-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(p) -CO-NR8-O-C1-4of alkyl,

(q) -NR6R7,

(r) -NR8-(CH2)n-OH,

(s) -NR8-(CH2)n-SO2-C1-4of alkyl,

(t) -NR8-CO-(optionally halogenated C1-4the alkyl),

(u) -NR8-CO-(CH2)n-OH (where the group (CH2)noptionally substituted by optionally halogenated C1-4the alkyl or hydroxy),

(v) -NR8-CO-(CH2)n -CN

(w) -NR8-CO-(CH2)n-NR6R7(when n is not less than 2, a subset-CH2CH2group (CH2)noptionally replaced by-CH=CH-),

(x) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(y) -NR8-CO-(CH2)n-SO-(optionally halogenated C1-4the alkyl),

(z) -NR8-CO-(CH2)n-SO2-(optionally halogenated C1-4the alkyl) (where the group (CH2)noptionally substituted C1-4by alkyl),

(aa) -NR8-CO-(CH2)n-SO2-C3-8cycloalkyl,

(bb) -NR8-CO-(CH2)n-NR8-SO2-C1-4of alkyl,

(cc) -NR8-CO2-(CH2)n-SO2-C1-4of alkyl,

(dd) -NR8-CO-NH-(CH2)n-SO2-C1-4of alkyl,

(ee) -NR8-CO-NH-O-C1-4of alkyl,

(ff) -NR8-CO-NH-(CH2)n-O-C1-4of alkyl,

(gg) -NR8-C(=NH)-NH-C1-4of alkyl,

(hh) -NR8-SO2-(CH2)n-SO2-C1-4of alkyl,

(ii) -S-(CH2)n-OH,

(jj) -SO-(CH2)n-OH,

(kk) -SO2-(CH2)n-OH, and

(ll) -NR8-CO-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and obazatelno oxidized sulfur atom, which is optionally substituted by substituent(s)selected(s) hydroxy, C1-4the alkyl, optionally oxidized C1-4alkylthio, -CO-C1-4of alkyl, -CO-O-C1-4of alkyl, -CO-NH-C1-4of alkyl, -CONH2, -SO2-C1-4of alkyl, -SO2-NH-C1-4of alkyl, -SO2NH2and the like),

where n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, and R8represents a hydrogen atom or a C1-4alkyl group,

(B) compound (I), where

W represents CR1;

A represents a phenyl-C1-3alkyloxy-C6-18aryl group, where the phenyl portion optionally substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4the alkyl and cyano, and

C6-18the aryl part is optionally substituted by 1-4 substituents selected from halogen, C1-4the alkyl, optionally containing hydroxy, and C1-4alkyloxy;

X1 represents-NR3'-where R3'represents a hydrogen atom or a C1-6alkyl group;

R1represents a

(i) a hydrogen atom,

(ii) C1-4alkyl group or a C2-4alkenylphenol group, each of which is optionally substituted by substituent(s)selected(the)

(a) hydroxy,

(b) amino,

(c) -NR8-CO-(CH2)n-NR6R7and

(d) -NR8-CO-(CH2)n-O-C1-4of alkyl,

where n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, R8represents a hydrogen atom or a C1-4alkyl group, and when n is not less than 2, a subset-CH2-CH2group (CH2)noptionally replaced by-CH=CH-, or

(iii) C6-18aryl group optionally substituted by substituent(s)selected(s)

(a) amino,

(b) carboxy, and

(c) -NR8-CO-(CH2)n-O-C1-4of alkyl, where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group, or

(iv) 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom; and

R2represents a

(i) a hydrogen atom,

(ii) C1-8alkyl group optionally substituted by substituent(s)selected(s)

(a) halogen,

(b) hydroxy,

(c) C1-4alkyloxy,

(d) -O-(CH2)n-OH,

(e) -O-(CH2)n-O-C1-4of alkyl,

(f) -CO-NR8-(CH2)n-OH,

(g) -NR6R7and

(h) -NR8-(CH2)n-OH,

where n is equal to a the th number from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, and R8represents a hydrogen atom or a C1-4alkyl group,

(iii) C6-18aryl-C1-4alkyl group optionally substituted by substituent(s)selected(s)

(a) C1-4the alkyl, optionally containing hydroxy,

(b) carboxy,

(c) C1-4alkoxycarbonyl,

(d) 5-8-membered heterocultural containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, which optionally has substituent(s)selected(e) of hydroxy and C1-4of alkyl, and

(e) C1-4allylcarbamate, optionally containing substituent(s)selected(e) of hydroxy and carbamoyl,

(iv) C6-18arylcarbamoyl group, optionally substituted C1-4alkoxy,

(v) C6-18arylsulfonyl group, optionally substituted C1-4alkoxy, or

(vi) 5-8-membered heterocycle-C1-4alkyl group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, which is optionally substituted by substituent(s)selected(s)

(a) carboxy, and

(b) C1-4alkoxycarbonyl; or

R2and R3'not necessarily related to the formation of C2-4alkylene,

(C) compound (I), where

W depict is to place a CR 1;

And is a 5-8-membered, heterocyclic-C6-18aryl group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, where heterocyclics-part optionally substituted by 1-5 substituents selected from the

(i) halogen,

(ii) C1-4of alkyl,

(iii) C1-4alkylcarboxylic,

(iv) optionally halogenated C1-4alkoxycarbonyl,

(v) C3-8cycloalkylcarbonyl and

(vi) carbamoyl group, optionally substituted by substituent(s)selected(s)

(a) optionally halogenated C1-8of alkyl,

(b) C3-8cycloalkyl and

(c) C6-18aryl, optionally substituted by substituent(s)selected(s) halogen, C1-4alkyl and C1-4alkyloxy, and

C6-18the aryl part is optionally substituted by 1-4 substituents selected from halogen and optionally halogenated C1-4of alkyl;

X1 represents-NR3'-where R3'represents a hydrogen atom or a C1-6alkyl group;

R1represents a

(i) a hydrogen atom,

(ii) C1-4alkyl group or a C2-4alkenylphenol group, each of which is optionally substituted by substituent(s)selected(s)

(a) hydroxy,

(b) amino,

(c) -NR8-CO-(CH2)n-NR6R7and

(d) -NR8-CO-(CH )n-O-C1-4of alkyl,

where n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, R8represents a hydrogen atom or a C1-4alkyl group, and when n is not less than 2, a subset-CH2CH2group (CH2)noptionally replaced by-CH=CH-,

(iii) C6-18aryl group optionally substituted by substituent(s)selected(s)

(a) C1-4the alkyl, optionally substituted by substituent(s)selected(s) hydroxy, -NR8-(CH2)n-SO2-C1-4the alkyl and-NR8-CO-(CH2)n-O-C1-4of alkyl,

(b) amino,

(c) C1-4alkyloxy,

(d) carboxy, and

(e) -NR8-CO-(CH2)n-O-C1-4of alkyl,

where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group, or

(iv) 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom; and

R2represents a

(i) a hydrogen atom,

(ii) C1-4alkyl group optionally substituted by substituent(s)selected(s)

(a) halogen,

(b) hydroxy,

(c) C1-4alkyloxy,

(d) carboxy,

(e) C1-4alkoxycarbonyl,

(f) -O-(CH2)n-H

(g) -O-(CH2)n-O-C1-4of alkyl,

(h) -CO-NR8-(CH2)n-OH, and

(i) -NR8-CO-(CH2)n-SO2-C1-4of alkyl,

where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group, or

(iii) C6-18aryl-C1-4alkyl group, optionally substituted C1-4the alkyl, optionally containing hydroxy; or

R2and R3'not necessarily related to the formation of C2-4alkylene,

(D) compound (I), where

W represents CR1;

A is a 5-8-membered heterocycle-C1-3alkyloxy-C6-18aryl group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, where C6-18the aryl part is optionally substituted with halogen;

X1 represents-NR3'-where R3'represents a hydrogen atom or a C1-6alkyl group;

R1represents a

(i) a hydrogen atom, or

(ii) 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom; and

R2represents a

(i) a hydrogen atom,

(ii) C1-4alkyl, optionally substituted by substituent(s)selected(s)

(a) C1-4alkyloxy,

(b) -O-(CH2)n-OH, and

(c) -NR8-CO-(CH2)n-SOsub> 2-C1-4of alkyl,

where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group, or

(iii) 5-8-membered heterocycle-C1-4alkyl group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, which is optionally substituted by substituent(s)selected(s)

(a) carboxy, and

(b) C1-4alkoxycarbonyl,

(E) compound (I), where

W represents N;

A represents phenyloxy-C6-18aryl group, where phenyloxy-part optionally substituted by 1-5 substituents selected from optionally halogenated C1-4the alkyl and cyano, and

C6-18the aryl part is optionally substituted by 1-4 substituents selected from halogen and C1-4of alkyl;

X1 represents-NR3'-where R3'represents a hydrogen atom or a C1-6alkyl group; and

R2represents a

(i) a hydrogen atom, or

(ii) C1-4alkyl group, optionally substituted-O-(CH2)n-OH, where n is an integer from 1 to 4

(F) compound (I), where

W represents N;

A represents a phenyl-C1-3alkyloxy-C6-18aryl group, where the phenyl portion optionally substituted by 1-5 substituents selected from halogen and cyano, and

C6-18aryl part machineavailable substituted by 1-4 substituents, selected from halogen and C1-4of alkyl;

X1 represents-NR3'-where R3'represents a hydrogen atom or a C1-6alkyl group; and

R2represents a

(i) a hydrogen atom,

(ii) C1-4alkyl group, optionally substituted by 1-5 substituents selected from the group consisting of

(a) hydroxy,

(b) -O-(CH2)n-OH,

(c) -NR8-(CH2)n-O-C1-4of alkyl,

(d) -NR8-(CH2)n-heterocyclic group (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom), and

(e) -NR8-(CH2)n-SO2-C1-4of alkyl, where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group,

(iii) C6-18aryl group, optionally substituted C1-4the alkyl, optionally substituted by substituent(s)selected(s) hydroxy, -NR8-(CH2)n-OH, -NR8-(CH2)n-heterocyclic group (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom) and-NR8-(CH2)n-SO2C 1-4the alkyl, or

(iv) C6-18aryl-C1-4alkyl group, optionally substituted by 1-5 substituents selected from the group consisting of

(a) carboxy,

(b) C1-4alkoxycarbonyl and

(c) -CO-NR8-(CH2)n-O-C1-4of alkyl, where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group; or

R2and R3'not necessarily related to the formation of C2-4alkylene,

(G) compound (I), where

W represents N;

And is a 5-8-membered, heterocyclic-C6-18aryl group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, where heterocyclics-part optionally substituted C1-4the alkyl and C6-18the aryl part is optionally substituted C1-4by alkyl;

X1 represents-NR3'-where R3'represents a hydrogen atom or a C1-6alkyl group; and

R2represents a

(i) a hydrogen atom,

(ii) C1-4alkyl group, optionally substituted hydroxy,

(iii) C6-18aryl group optionally substituted by substituent(s)selected(s)

(a) nitro,

(b) amino,

(c) -CO-NR8-(CH2)n-O-C1-4of alkyl,

(d) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(e) -NR8-CO-(CH2)n-NR6 R7,

(f) -NR8-CO-(CH2)n-COOH

(g) -NR8-CO-(CH2)n-CO2-C1-4the alkyl and

(h) -NR8-CO-(CH2)m-O-(CH2)n-O-C1-4of alkyl,

where m is an integer from 0 to 4, n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, and R8represents a hydrogen atom or a C1-4alkyl group, or

(iv) C6-18aryl-C1-4alkyl group optionally substituted by substituent(s)selected(s)

(a) carboxy,

(b) C1-4alkoxycarbonyl,

(c) -CO-NR8-(CH2)n-O-C1-4of alkyl, where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group); or

R2and R3'not necessarily related to the formation of C2-4alkylene,

(H) compound (I), where

W represents CH;

A represents a C6-18aryl group optionally substituted by substituent(s)selected(s)

(a) carboxy,

(b) C1-4alkoxycarbonyl,

(c) 5-8-membered heterocyclimamines group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom (preferably 5-8-membered cyclic aminocarbonyl group, optionally containing 1 or 2 g is teratoma, selected from nitrogen atom, oxygen atom and sulfur atom, which optionally substituted C6-18aryl-C1-4by alkyl;

(d) carbamoyl group, optionally substituted C6-18aryl-C1-4the alkyl, and

(e) raidgroup, optionally substituted C6-18aryl-C1-4by alkyl;

X1 represents-NR3'-where R3'represents a hydrogen atom or a C1-6alkyl group; and

R2represents a hydrogen atom,

[58] the compound according to above item [1], where a is a (i) C6-18aryl group, or (ii) 5-8-membered heteroaryl group containing, as an atom (atom in the ring)of the cyclic system, 1-4 heteroatoms, selected from oxygen atom, optionally oxidized sulfur atom and a nitrogen atom (preferably oxygen atom, sulfur atom and nitrogen atom), each of which is optionally substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4of alkyl, hydroxy, optionally halogenated C1-4alkyloxy, C1-4allyloxymethyl, hydroxy-C1-4of alkyl, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl, C1-4alkylsulfonamides and a group of the formula-Y2/sup> -B, where Y2represents a single bond, -O-, -O-(C1-3alkylene)-, -NH - or-S-,

B represents

(A) (i) C6-18aryl group, (ii) 5-8-membered heteroaryl group containing, as an atom (atom in the ring)of the cyclic system, 1-4 heteroatoms, selected from oxygen atom, optionally oxidized sulfur atom and a nitrogen atom (preferably oxygen atom, sulfur atom and nitrogen atom)or a saturated or unsaturated aliphatic heterocyclic group, (iii) C3-8cycloalkyl group, (iv) karbamoilnuyu group, (v) C6-18arylcarbamoyl group or (vi) C6-18aryl-C1-4alkylcarboxylic group, each of which is optionally substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4of alkyl, hydroxy, optionally halogenated C1-4alkyloxy, C1-4allyloxymethyl, hydroxy-C1-4of alkyl, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonyl, or

(B) raidgroup, optionally containing 1 or 2 C1-8alkyl group optionally substituted by substituent(s)selected(s) from the group T substituents,

where raidgroup contains two replacement the Titel and they optionally form, together with the adjacent nitrogen atom, a 3-8-membered saturated or unsaturated aliphatic heterocyclic group, optionally substituted by substituent(s)selected(s) from the group T substituents,

where the group T substituents is a group of

(a) halogen,

(b) oxo,

(c) optionally halogenated C1-4of alkyl,

(d) -(CH2)m-Q,

(e) -(CH2)m-Z1-(optionally halogenated C1-4the alkyl),

(f) -(CH2)m-Z1-C3-8cycloalkyl,

(g) -(CH2)m-Z2-(CH2)n-Q,

(h) -(CH2)m-Z2-(CH2)n-Z1-(optionally halogenated C1-4the alkyl),

(i) -(CH2)m-Z2-(CH2)n-Z1-C3-8cycloalkyl,

(j) -(CH2)m-Z1-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom),

(k) -(CH2)m-Z2-C1-4alkoxy and

(l) -(CH2)m-Z2-(CH2)n-Z1-(CH2)n-Z1-C1-4of alkyl,

where m is an integer from 0 to 4, n is an integer from 1 to 4

Q represents the Wallpaper hydroxy, carboxy, cyano, nitro, -NR6R7, -CONR6R7, -OCONH2or-SO2NR6R7,

Z1 represents-O-, -CO-, -C(OH)R8-, -C(=N-OR8)-, -S-, -SO-, -SO2-, -N(COR8)-, -N(CO2R9)-, -N(SO2R9)-, -CO-O-, -O-CO-, -CO-NR8-, -NR8-CO-, -NR8-CO2-, -NR8-CO-NH-, -NR8-SO2- or-NR8-C(=NH)-NH-,

Z2 represents-O-, -CO-, -C(OH)R8-, -C(=N-OR8)-, -S-, -SO-, -SO2-, -NR8-, -N(COR8)-, -N(CO2R9)-, -N(SO2R9)-, -CO-O-, -O-CO-, -CO-NR8-, -NR8-CO-, -NR8-CO2-, -NR8-CO-NH-, -NR8-C(=NH)-NH-, -NR8-SO2- or-SO2-NR8-,

(CH2)mand (CH2)noptionally substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4of alkyl and hydroxy, and when m or n is not less than 2, a subset-CH2CH2groups (CH2)m and (CH2)noptionally replaced by-CH=CH - or-C≡C-,

R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, or R6and R7form, together with the nitrogen atom, a 3-8-membered saturated or unsaturated aliphatic heterocyclic group, optionally substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4of alkyl, is hydroxy, optionally halogenated C1-4alkyloxy, C1-4allyloxymethyl, hydroxy, C1-4of alkyl, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonamides,

R8represents a hydrogen atom or a C1-4alkyl, and R9represents a C1-4alkyl,

R3represents (i) hydrogen atom, or

(ii) C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group or a C3-8cycloalkyl group, each of which is optionally substituted by 1-3 substituents selected from halogen, hydroxy, C1-4alkyloxy, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonyl, or

R3not necessarily associated with carbon atom or a heteroatom in the aryl group or the heteroaryl group represented by A, with the formation of a saturated or unsaturated 4-to 8-membered nitrogen-containing heterocycle, which optionally is substituted by 1-3 substituents selected from halogen, hydroxy, C1-4alkyloxy, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl is, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonamides,

Y1represents a

(i) single bond or

(ii) C1-4alkylene or-O-(C1-4alkylene)-, each of which is optionally substituted by 1-3 substituents selected from halogen, hydroxy, C1-4alkyloxy, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonamides,

R1represents a

(i) a hydrogen atom, or

(ii) a group represented by formula-X2-R4where X2represents a single bond, -NH - or-O-, and R4represents a

(i) a hydrogen atom,

(ii) cyano,

(iii) C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, C1-8alkylcarboxylic group, C3-8cycloalkyl group, C6-18aryl group, a C6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, heterocyclic group (e.g., 5-8-membered heteroaryl group containing, as an atom (atom in the ring)of the cyclic system, 1-4 heteroatoms selected from the ATO is and oxygen, optionally oxidized sulfur atom and a nitrogen atom (preferably oxygen atom, sulfur atom and nitrogen atom)or a saturated or unsaturated aliphatic heterocyclic group), a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted by 1-5 substituents selected from the group T substituents, or

(iv) karbamoilnuyu group, optionally containing 1 or 2 C1-8alkyl group optionally substituted by substituent(s)selected(s) from the group T substituents,

where carnemolla group contains two deputies and they optionally form, together with the adjacent nitrogen atom, a 3-8-membered saturated or unsaturated aliphatic heterocyclic group, optionally substituted by substituent(s)selected(s) from the group T substituents,

R2represents a

(i) a hydrogen atom,

(ii) C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, C1-8alkylcarboxylic group, C1-8alkylsulfonyl group, C3-8cycloalkyl group, C6-18aryl group, a C6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, C6-18arylsulfonyl group gets riikliku group, a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted by 1-5 substituents selected from the group T substituents, or

(iii) karbamoilnuyu group, optionally containing 1 or 2 C1-8alkyl group optionally substituted by substituent(s)selected(s) from the group T substituents,

where carnemolla group contains two deputies and they optionally form, together with the adjacent nitrogen atom, a 3-8-membered saturated or unsaturated aliphatic heterocyclic group, which is optionally substituted by substituent(s)selected(s) from the group T substituents, or

R1and R2or R2and R3not necessarily related with the formation of a saturated or unsaturated 4-to 8-membered heterocycle, optionally substituted by 1-5 substituents selected from the group T substituents,

[59] the compound according to above item [15], where

R1arepresents (i) hydrogen atom, or

(ii) a group represented by formula-X2-R4where X2represents a single bond, -NH - or-O-, and R4represents a

(i) a hydrogen atom,

(ii) cyano,

(iii) C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, C1-8al is ylcarbonyl group, C3-8cycloalkyl group, C6-18aryl group, a C6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, heterocyclic group (e.g., 5-8-membered heteroaryl group containing, as an atom (atom in the ring)of the cyclic system, 1-4 heteroatoms, selected from oxygen atom, optionally oxidized sulfur atom and a nitrogen atom (preferably oxygen atom, sulfur atom and nitrogen atom)or a saturated or unsaturated aliphatic heterocyclic group), a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted by 1-5 substituents selected from the group T substituents, or

(iv) karbamoilnuyu group, optionally containing 1 or 2 C1-8alkyl group optionally substituted by substituent(s)selected(s) from the group T substituents,

where carnemolla group contains two deputies and they optionally form, together with the adjacent nitrogen atom, a 3-8-membered saturated or unsaturated aliphatic heterocyclic group, which is optionally substituted by substituent(s)selected(s) from the group T substituents,

R2arepresents a

(i) a hydrogen atom,

1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, C1-8alkylcarboxylic group, C1-8alkylsulfonyl group, C3-8cycloalkyl group, C6-18aryl group, a C6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, C6-18arylsulfonyl group, heterocyclic group, a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted by 1-5 substituents selected from the group T substituents, or

(iii) karbamoilnuyu group, optionally containing 1 or 2 C1-8alkyl group optionally substituted by substituent(s)selected(s) from the group T substituents,

where carnemolla group contains two deputies and they optionally form, together with the adjacent nitrogen atom, a 3-8-membered saturated or unsaturated aliphatic heterocyclic group, which is optionally substituted by substituent(s)selected(s) from the group T substituents, or

R1aand R2aor R2aand R3anot necessarily related with the formation of a saturated or unsaturated 4-to 8-membered heterocycle, optionally substituted by 1-5 substituents selected from the group T to cover the oil,

R3arepresents a

(i) a hydrogen atom, or

(ii) C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group or a C3-8cycloalkyl group, each of which is optionally substituted by 1-3 substituents selected from halogen, hydroxy, C1-4alkyloxy, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonyl, or

R3anot necessarily linked to the carbon atom of the adjacent phenyl group with the formation of a saturated or unsaturated 4-to 8-membered nitrogen-containing heterocycle, which optionally is substituted by 1-3 substituents selected from halogen, hydroxy, C1-4alkyloxy, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonamides,

Barepresents a benzene ring, optionally substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4of alkyl, hydroxy, optionally halogenated C1-4alkyloxy, C1-4allyloxymethyl, hydroxy-C1-4of alkyl, C1-4alkylsulphonyl, carboxy, C1-4is alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonamides, and

Carepresents a C6-18aryl group, optionally substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4of alkyl, hydroxy, optionally halogenated C1-4alkyloxy, C1-4allyloxymethyl, hydroxy-C1-4of alkyl, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonamides,

[60] the compound according to above item [16], where

R1brepresents (i) hydrogen atom, or

(ii) a group represented by formula-X2-R4where X2represents a single bond, -NH - or-O-, and R4represents a

(i) a hydrogen atom,

(ii) cyano,

(iii) C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, C1-8alkylcarboxylic group, C3-8cycloalkyl group, C6-18aryl group, a C6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, heterocyclic group (e.g., 5-8-membered heteroaryl the ing group, containing, as an atom (atom in the ring)of the cyclic system, 1-4 heteroatoms, selected from oxygen atom, optionally oxidized sulfur atom and a nitrogen atom (preferably oxygen atom, sulfur atom and nitrogen atom)or a saturated or unsaturated aliphatic heterocyclic group), a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted by 1-5 substituents selected from the group T substituents, or

(iv) karbamoilnuyu group, optionally containing 1 or 2 C1-8alkyl group optionally substituted by substituent(s)selected(s) from the group T substituents,

where carnemolla group contains two deputies and they optionally form, together with the adjacent nitrogen atom, a 3-8-membered saturated or unsaturated aliphatic heterocyclic group, which is optionally substituted by substituent(s)selected(s) from the group T substituents,

R2brepresents a

(i) a hydrogen atom,

(ii) C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, C1-8alkylcarboxylic group, C1-8alkylsulfonyl group, C3-8cycloalkyl group, C6-18aryl group, a C6-18aryl-C1-4alkyl g is the SCP, C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, C6-18arylsulfonyl group, heterocyclic group, a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted by 1-5 substituents selected from the group T substituents, or

(iii) karbamoilnuyu group, optionally containing 1 or 2 C1-8alkyl group optionally substituted by substituent(s)selected(s) from the group T substituents,

where carnemolla group contains two deputies and they optionally form, together with the adjacent nitrogen atom, a 3-8-membered saturated or unsaturated aliphatic heterocyclic group, which is optionally substituted by substituent(s)selected(s) from the group T substituents, or

R1band R2bor R2band R3bnot necessarily related with the formation of a saturated or unsaturated 4-to 8-membered heterocycle, optionally substituted by 1-5 substituents selected from the group T substituents,

R3brepresents (i) hydrogen atom, or

(ii) C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group or a C3-8cycloalkyl group, each of which is optionally substituted by 1-3 substituents, wybran the mi from halogen, hydroxy, C1-4alkyloxy, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonyl, or

R3bnot necessarily linked to the carbon atom of the adjacent phenyl group with the formation of a saturated or unsaturated 4-to 8-membered heterocycle, which optionally is substituted by 1-3 substituents selected from halogen, hydroxy, C1-4alkyloxy, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonamides,

Bbrepresents a benzene ring, optionally substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4of alkyl, hydroxy, optionally halogenated C1-4alkyloxy, C1-4allyloxymethyl, hydroxy-C1-4of alkyl, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonamides,

Cbrepresents a C6-18aryl group, optionally substituted by 1-5 substituents selected from a halogen, n is necessarily halogenated C 1-4of alkyl, hydroxy, optionally halogenated1-4alkyloxy, C1-4allyloxymethyl, hydroxy-C1-4of alkyl, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonamides, and

Zbrepresents a C1-3alkylenes group, optionally substituted by 1-3 substituents selected from halogen, hydroxy, C1-4alkyloxy, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonamides,

[61] the compound according to above item [17], where

R1crepresents (i) hydrogen atom, or

(ii) a group represented by formula-X2-R4where X2represents a single bond, -NH - or-O - and R4represents a

(i) a hydrogen atom,

(ii) cyano,

(iii) C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, C1-8alkylcarboxylic group, C3-8cycloalkyl group, C6-18aryl group, a C6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, heterocyclics group (for example, 5-8-membered heteroaryl group containing, as an atom (atom in the ring)of the cyclic system, 1-4 heteroatoms, selected from oxygen atom, optionally oxidized sulfur atom and a nitrogen atom (preferably oxygen atom, sulfur atom and nitrogen atom)or a saturated or unsaturated aliphatic heterocyclic group), a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted by 1-5 substituents selected from the group T substituents, or

(iv) karbamoilnuyu group, optionally containing 1 or 2 C1-8alkyl group optionally substituted by substituent(s)selected(s) from the group T substituents,

where carnemolla group contains two deputies and they optionally form, together with the adjacent nitrogen atom, a 3-8-membered saturated or unsaturated aliphatic heterocyclic group, which is optionally substituted by substituent(s)selected(s) from the group T substituents,

R2crepresents a

(i) a hydrogen atom,

(ii) C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, C1-8alkylcarboxylic group, C1-8alkylsulfonyl group, C3-8cycloalkyl group, C6-18aryl group, a C 6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, C6-18arylsulfonyl group, heterocyclic group, a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted by 1-5 substituents selected from the group T substituents, or

(iii) karbamoilnuyu group, optionally containing 1 or 2 C1-8alkyl group optionally substituted by substituent(s)selected(s) from the group T substituents,

where carnemolla group contains two deputies and they optionally form, together with the adjacent nitrogen atom, a 3-8 membered saturated or unsaturated aliphatic heterocyclic group, which is optionally substituted by substituent(s)selected(s) from the group T substituents, or

R1cand R2cor R2cand R3cnot necessarily related with the formation of a saturated or unsaturated 4-to 8-membered heterocycle, optionally substituted by 1-5 substituents selected from the group T substituents,

R3crepresents (i) hydrogen atom, or

(ii) C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group or a C3-8cycloalkyl group, each of neobythites is but substituted by 1-3 substituents, selected from halogen, hydroxy, C1-4alkyloxy, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonyl, or

R3cnot necessarily linked to the carbon atom of the adjacent phenyl group with the formation of a saturated or unsaturated 4-to 8-membered nitrogen-containing heterocycle, which optionally is substituted by 1-3 substituents selected from halogen, hydroxy, C1-4alkyloxy, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonamides,

Bcrepresents a benzene ring, optionally substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4of alkyl, hydroxy, optionally halogenated1-4alkyloxy, C1-4allyloxymethyl, hydroxy-C1-4of alkyl, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonamides, and

Ccis a 5-8-membered heterocyclic group containing 1-3 GE is Euroatom, selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, which optionally is substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4of alkyl, hydroxy, optionally halogenated1-4alkyloxy, C1-4allyloxymethyl, hydroxy-C1-4of alkyl, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonamides,

[62] the compound according to above item [18], where

R1drepresents (i) hydrogen atom, or

(ii) a group represented by formula-X2-R4where X2represents a single bond, -NH - or-O - and R4represents a

(i) a hydrogen atom,

(ii) cyano,

(iii) C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, C1-8alkylcarboxylic group, C3-4alkyl group, a C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, heterocyclic group (e.g., 5-8-membered heteroaryl group containing, as an atom (atom in the ring)of the cyclic system, 1-4 heteroatoms, selected from oxygen atom, optionally oxidized sulfur atom and atom I is the (preferably oxygen atom, the sulfur atom and nitrogen atom)or a saturated or unsaturated aliphatic heterocyclic group), a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted by 1-5 substituents selected from the group T substituents, or

(iv) karbamoilnuyu group, optionally containing 1 or 2 C1-8alkyl group optionally substituted by substituent(s)selected(s) from the group T substituents,

where carnemolla group contains two deputies and they optionally form, together with the adjacent nitrogen atom, a 3-8-membered saturated or unsaturated aliphatic heterocyclic group, which is optionally substituted by substituent(s)selected(s) from the group T substituents,

R2drepresents a

(i) a hydrogen atom,

(ii) C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, C1-8alkylcarboxylic group, C1-8alkylsulfonyl group, C3-8cycloalkyl group, C6-18aryl group, a C6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, C6-18arylsulfonyl group, heterocyclic group, a heterocycle-C1-4alkyl group, heterocultural the function group or a heterocycle-C 1-4alkylcarboxylic group, each of which is optionally substituted by 1-5 substituents selected from the group T substituents, or

(iii) karbamoilnuyu group, optionally containing 1 or 2 C1-8alkyl group optionally substituted by substituent(s)selected(s) from the group T substituents,

where carnemolla group contains two deputies and they optionally form, together with the adjacent nitrogen atom, a 3-8-membered saturated or unsaturated aliphatic heterocyclic group, which is optionally substituted by substituent(s)selected(s) from the group T substituents, or

R1dand R2dor R2dand R3dnot necessarily related with the formation of a saturated or unsaturated 4-to 8-membered heterocycle, which optionally is substituted by 1-5 substituents selected from the group T substituents,

R3drepresents a

(i) a hydrogen atom, or

(ii) C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group or a C3-8cycloalkyl group, each of which is optionally substituted by 1-3 substituents selected from halogen, hydroxy, C1-4alkyloxy, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4Alki is sulfonylamino, or

R3dnot necessarily linked to the carbon atom of the adjacent phenyl group with the formation of a saturated or unsaturated 4-to 8-membered nitrogen-containing heterocycle, which optionally is substituted by 1-3 substituents selected from halogen, hydroxy, C1-4alkyloxy, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonamides,

Bdrepresents a benzene ring, optionally substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4of alkyl, hydroxy, optionally halogenated1-4alkyloxy, C1-4allyloxymethyl, hydroxy-C1-4of alkyl, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonamides,

Cdis a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, which optionally is substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4of alkyl, hydroxy, optionally of halogenerator is th 1-4alkyloxy, C1-4allyloxymethyl, hydroxy-C1-4of alkyl, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonamides, and

Zdrepresents a C1-3alkylenes group, optionally substituted by 1-3 substituents selected from halogen, hydroxy, C1-4alkyloxy, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonamides,

[63] the compound according to above item [19], where

R2erepresents a

(i) a hydrogen atom,

(ii) C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, C1-8alkylcarboxylic group, C1-8alkylsulfonyl group, C3-8cycloalkyl group, C6-18aryl group, a C6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, C6-18arylsulfonyl group, heterocyclic group, a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optional is entrusted substituted by 1-5 substituents, selected from the group T substituents, or

(iii) karbamoilnuyu group, optionally containing 1 or 2 C1-8alkyl group optionally substituted by substituent(s)selected(s) from the group T substituents,

where carnemolla group contains two deputies and they optionally form, together with the adjacent nitrogen atom, a 3-8-membered saturated or unsaturated aliphatic heterocyclic group, which is optionally substituted by substituent(s)selected(s) from the group T substituents, or

R2eand R3enot necessarily related with the formation of a saturated or unsaturated 4-to 8-membered heterocycle, optionally substituted by 1-5 substituents selected from the group T substituents,

R3erepresents (i) hydrogen atom, or

(ii) C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group or a C3-8cycloalkyl group, each of which is optionally substituted by 1-3 substituents selected from halogen, hydroxy, C1-4alkyloxy, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonyl, or

R3enot necessarily linked to the carbon atom of the adjacent phenyl group with the formation saturated with the CSO or unsaturated 4-to 8-membered nitrogen-containing heterocycle, which is optionally substituted by 1-3 substituents selected from halogen, hydroxy, C1-4alkyloxy, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonamides,

Berepresents a benzene ring, optionally substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4of alkyl, hydroxy, optionally halogenated1-4alkyloxy, C1-4allyloxymethyl, hydroxy-C1-4of alkyl, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonamides, and

Cerepresents a C6-18aryl group, optionally substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4of alkyl, hydroxy, optionally halogenated1-4alkyloxy, C1-4allyloxymethyl, hydroxy-C1-4of alkyl, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonamides,

[64] the compounds is their on the above item [20], where

R2frepresents a

(i) a hydrogen atom,

(ii) C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, C1-8alkylcarboxylic group, C1-8alkylsulfonyl group, C3-8cycloalkyl group, C6-18aryl group, a C6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, C6-18arylsulfonyl group, heterocyclic group, a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted by 1-5 substituents selected from the group T substituents, or

(iii) karbamoilnuyu group, optionally containing 1 or 2 C1-8alkyl group optionally substituted by substituent(s)selected(s) from the group T substituents,

where carnemolla group contains two deputies and they optionally form, together with the adjacent nitrogen atom, a 3-8-membered saturated or unsaturated aliphatic heterocyclic group, which is optionally substituted by substituent(s)selected(s) from the group T substituents, or

R2fand R3fnot necessarily related with the formation of a saturated or unsaturated 4-to 8-membered heterocycle, optionally substituted by 1-5 what zamestitelyami, selected from the group T substituents,

R3frepresents (i) hydrogen atom, or

(ii) C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group or a C3-8cycloalkyl group, each of which is optionally substituted by 1-3 substituents selected from halogen, hydroxy, C1-4alkyloxy, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonyl, or

R3fnot necessarily linked to the carbon atom of the adjacent phenyl group with the formation of a saturated or unsaturated 4-to 8-membered nitrogen-containing heterocycle, which optionally is substituted by 1-3 substituents selected from halogen, hydroxy, C1-4alkyloxy, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonamides,

Bfrepresents a benzene ring, optionally substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4of alkyl, hydroxy, optionally halogenated1-4alkyloxy, C1-4allyloxymethyl, hydroxy-C1-4of alkyl, C1-4and what of kilcarbery, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonamides,

Cfrepresents a C6-18aryl group, optionally substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4of alkyl, hydroxy, optionally halogenated1-4alkyloxy, C1-4allyloxymethyl, hydroxy-C1-4of alkyl, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonamides,

Zfrepresents a C1-3alkylenes group, optionally substituted by 1-3 substituents selected from halogen, hydroxy, C1-4alkyloxy, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonamides,

[65] the compound according to above item [21], where

R2grepresents a

(i) a hydrogen atom,

(ii) C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, C1-8alkylcarboxylic group, C1-8alkylsulfonyl groups who, C3-8cycloalkyl group, C6-18aryl group, a C6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, C6-18arylsulfonyl group, heterocyclic group, a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted by 1-5 substituents selected from the group T substituents, or

(iii) karbamoilnuyu group, optionally containing 1 or 2 C1-8alkyl group optionally substituted by substituent(s)selected(s) from the group T substituents,

where carnemolla group contains two deputies and they optionally form, together with the adjacent nitrogen atom, a 3-8-membered saturated or unsaturated aliphatic heterocyclic group, which is optionally substituted by substituent(s)selected(s) from the group T substituents, or

R2gand R3gnot necessarily related with the formation of a saturated or unsaturated 4-to 8-membered heterocycle, optionally substituted by 1-5 substituents selected from the group T substituents,

R3grepresents (i) hydrogen atom, or

(ii) C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group or a C3-8cycloalkyl the th group, each of which optionally is substituted by 1-3 substituents selected from halogen, hydroxy, C1-4alkyloxy, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonyl, or

R3gnot necessarily linked to the carbon atom of the adjacent phenyl group with the formation of a saturated or unsaturated 4-to 8-membered nitrogen-containing heterocycle, optionally substituted by 1-3 substituents selected from halogen, hydroxy, C1-4alkyloxy, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonamides,

Bgrepresents a benzene ring, optionally substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4of alkyl, hydroxy, optionally halogenated1-4alkyloxy, C1-4allyloxymethyl, hydroxy-C1-4of alkyl, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonamides,

Cgis Soboh the 5-8-membered heterocyclic group, containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, which optionally is substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4of alkyl, hydroxy, optionally halogenated1-4alkyloxy, C1-4allyloxymethyl, hydroxy-C1-4of alkyl, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonyl and the like.

In accordance with the present invention may be offered a condensed pyrimidine derivative, providing excellent inhibitory effect on tyrosinekinase, which is non-lethal and highly satisfactory as a pharmaceutical product, its production method and its application.

In this description, unless otherwise specified, “aryl” in the “aryl group” and the substituents include monocyclic aryl group and a condensed polycyclic aryl group. As the “aryl group”, you can specify, for example, C6-18aryl group. As “C6-18aryl group, you can specify, for example, phenyl, biphenylyl, naphthyl, antril, tenantry and acenaphthylene.

In this described and, as the “heterocyclic group” (and “heterocycle” in the substituents), you can specify, for example, 5-8-membered heteroaryl group or a saturated or unsaturated aliphatic heterocyclic group containing, as an atom (atom in the ring)of the cyclic system, one or more, preferably 1-4, more preferably 1 or 2) heteroatoms selected from oxygen atom, optionally oxidized sulfur atom and a nitrogen atom and the like (preferably oxygen atom, sulfur atom and nitrogen atom, and so on).

In this description, unless otherwise specified, as the “aliphatic hydrocarbon group”, you can specify an unbranched or branched aliphatic hydrocarbon group containing 1-15 carbon atoms, preferably 1-8 carbon atoms). As such the “aliphatic hydrocarbon group”, you can specify, for example, C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, C3-8cycloalkyl group and the like.

In this description, unless otherwise specified, as the “heteroaryl group”, you can specify monocyclic heterocyclic group (for example, 5 - or 6-membered aromatic monocyclic heterocyclic group such as furyl, thienyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolin, imide who was Salil, pyrazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, furazane, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl and the like) and aromatic condensed heterocyclic group (e.g., 8-12-membered aromatic condensed heterocyclic group such as benzofuranyl, isobenzofuranyl, benzothiazyl, indolyl, isoindolyl, 1H-indazole, begindetail, benzoxazolyl, 1,2-benzisoxazole, benzothiazole, benzopyranyl, 1,2-benzisothiazolin, 1H-benzotriazolyl, hinely, ethanolic, cinnoline, hintline, pinoxaden, phthalazine, naphthyridine, purinol, pteridinyl, carbazolyl, α-carbonyl, β-carbolines, γ-carbolines, acridines, phenoxazines, phenothiazines, phenazines, phenoxathiin, thianthrene, phenetidines, fantrainer, indolizinyl, pyrrolo[1,2-b]pyridazinyl, pyrazolo[1,5-a]pyridyl, imidazo[1,2-a]pyridyl, imidazo[1,5-a]pyridyl, imidazo[1,2-b]pyridazinyl, imidazo[1,2-a]pyrimidinyl, 1,2,4-triazolo[4,3-a]pyridyl, 1,2,4-triazolo[4,3-b]pyridazinyl and the like) and the like. As an aromatic condensed heterocyclic group are preferred heterocycle, where the above 5 - or 6-membered aromatic monocyclic heterocyclic group fused with benzol the first ring, and heterocycle, where the condensed two, identical or different, heterocycle above 5 - or 6-membered aromatic monocyclic heterocyclic group.

In this description, unless otherwise specified, as the “aliphatic heterocyclic group”, you can specify, for example, 3-8-membered (preferably 5 - or 6-membered) saturated or unsaturated (preferably saturated) aliphatic heterocyclic group, such as oxiranyl, azetidine, oxetane, titanyl, pyrrolidinyl, tetrahydrofuryl, tylenol, piperidyl, tetrahydropyranyl, morpholinyl, thiomorpholine, piperazinil, dihydro-1,2,4-oxadiazolyl and the like, and the like.

In this description, unless otherwise specified, as the “C1-8alkyl group, you can specify, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, tert-pentyl, neopentyl, n-hexyl, isohexyl, n-heptyl and n-octyl and the like, preferably C1-6alkyl group. In this description, in addition, unless otherwise indicated as “C1-4alkyl group, you can specify, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl and isobutyl.

In this description, unless otherwise specified, as the “C2-8alkenylphenol group, you can specify, for example, vinyl, (1 - or 2-)propenyl, (1-, 2 - or 3-)butenyl, penten is l, octenal and (1,3-)butadienyl, preferably C2-4alkenylphenol group.

In this description, unless otherwise specified, as the “C2-8alkenylphenol group, you can specify, for example, ethinyl, (1 - or 2-PROPYNYL, (1-, 2 - or 3-)butenyl, pentenyl and octenyl, preferably C2-4alkylamino group.

In this description, unless otherwise specified, as the “C3-8cycloalkyl group, you can specify, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl, preferably C3-6cycloalkyl group.

In this description, unless otherwise specified, as the “C1-4alkylene” you can specify, for example, methylene, ethylene, trimethylene, tetramethylene and propylene, and the like.

In this description, unless otherwise specified, as the “-O-(C1-4alkylene)-you can specify, for example, -OCH2-, -OCH2CH2-, -O(CH2)3-, -O(CH2)4-, -OCH(CH3)-, -OC(CH3)2-, -OCH(CH3)CH2-, -OCH2CH(CH3)-, -OC(CH3)2CH2- and-OCH2C(CH3)2- and the like.

In this description, unless otherwise specified, as the “C6-18arylcarbamoyl group, you can specify, for example, benzoyl, Naftoli, anticarbon, financecarbon and acenaphthenequinone, and the like.

In this description, unless otherwise specified, as the “C 6-18aryl-C1-4alkylcarboxylic group, you can specify, for example, benzylcarbamoyl, 3-phenylpropionyl, 2-phenylpropionyl, 4-phenylbutyl and 5-phenylpentane and the like.

In this description, unless otherwise specified, as the “halogen”, you can specify, fluorine, chlorine, bromine and iodine.

As a 5-8-membered heterocyclimamines group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom,” is preferable to “5-8-membered cyclic aminocarbonyl group, optionally containing 1 or 2 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom,” for example, you can specify pyrrolidin-1-ylcarbonyl, piperidine-1-ylcarbonyl, piperazine-1-ylcarbonyl, morpholine-4-ylcarbonyl, thiomorpholine-4-ylcarbonyl and the like.

In the above formula as the “aryl group” is preferable for A C6-18aryl group, and more preferred is phenyl.

“Aryl group” optionally substituted by a group of the formula-Y2-B, where Y2represents a single bond, -O-, -O-(C1-3alkylen)- (preferably-OCH2-), -NH - or-S-; b is an aryl group, a heterocyclic group, a C3-8cycloalkyl group, carbamoyl group, raidgroup, C6-18arylcarbamoyl group or a C6-18aryl-C1-4alkyl is ebonyjoy group, each of which is optionally substituted.

As Y2preferred is a single bond, -O -, or-OCH2and a more preferred group of-O -, or-OCH2-.

As the “aryl group” for B is preferred to C6-18aryl group, and more preferred is phenyl.

As the “heterocyclic group” for B preferred is the above “5-or 6-membered aromatic monocyclic heterocyclic group, and more preferred is pyridyl.

“Aryl group”, “heterocyclic group”, “C6-18arylcarbamoyl group” or “C6-18aryl-C1-4acylcarnitine group” for B may contain, for example, 1 to 5 same or different substituents selected from halogen, optionally halogenated C1-4of alkyl, hydroxy, optionally halogenated1-4alkyloxy, C1-4allyloxymethyl, hydroxy-C1-4of alkyl, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonamides, at any substitutable position(s).

“Aryl group” And may contain, other than that specified in the above group of the formula-Y2-B, 1-5 identical or different what's the substituents at any substitutable position(s). As such substituents can be specified substituents, such as those listed as examples of the “aryl group” or “heterocyclic group” for b

As the “aliphatic hydrocarbon group” for R3preferred are C1-8alkyl group, a C2-8Alchemilla group, C2-8Alchemilla group and C3-8cycloalkyl group.

“Aliphatic hydrocarbon group” for R3optionally substituted by 1-3 substituents selected from halogen, hydroxy, C1-4alkyloxy, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonamides.

“C1-4alkylene” and “-O-(C1-4alkylen)-for Y1optionally substituted by 1-3 substituents selected from halogen, hydroxy, C1-4alkyloxy, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonamides.

As X1preferred is a group-NR3-where R3is the same as defined above.

As the “optionally substituted group attached through a carbon atom,a nitrogen atom or an oxygen atom”, for R1you can specify a group of the formula-X2-R4where X2represents a single bond, -NH - or-O - and R4represents a hydrogen atom, cyano or C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, karbamoilnuyu group, C1-8alkylcarboxylic group, C3-8cycloalkyl group, C6-18aryl group, a C6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, heterocyclic group, a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted.

“C1-8alkyl group”, “C2-8Alchemilla group”, “C2-8Alchemilla group”, “C1-8acylcarnitine group”, “C3-8cycloalkyl group”, “C6-18aryl group”, “C6-18aryl-C1-4alkyl group”, “C6-18arylcarbamoyl group”, “C6-18aryl-C1-4acylcarnitine group”, “heterocyclic group”, “heterocycle-C1-4alkyl group”, “getrollbackonly group” and “heterocycle-C1-4acylcarnitine group optionally substituted, for example, one or more (preferably 1-5, more preferably 1-3) to cover the firs, selected from the

(a) halogen,

(b) oxo,

(c) optionally halogenated C1-4of alkyl,

(d) -(CH2)m-Q,

(e) -(CH2)m-Z1-(optionally halogenated C1-4the alkyl),

(f) -(CH2)m-Z1-C3-8cycloalkyl,

(g) -(CH2)m-Z2-(CH2)n-Q,

(h) -(CH2)m-Z2-(CH2)n-Z1-(optionally halogenated C1-4the alkyl),

(i) -(CH2)m-Z2-(CH2)n-Z1-C3-8cycloalkyl,

(j) -(CH2)m-Z1-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom),

(k) -(CH2)m-Z2-C1-4alkoxy and

(l) -(CH2)m-Z2-(CH2)n-Z1-(CH2)n-Z1-C1-4the alkyl (hereinafter these substituents is sometimes called the group T substituents).

In these formulas, m is an integer from 0 to 4, n is an integer from 1 to 4, Q represents hydroxy, carboxy, cyano, nitro, -NR6R7, -CONR6R7or-SO2NR6R7, Z1 represents-O-, -CO-, -C(OH)R8-, -C(=N-OR8-, -S-, -SO-, -SO2-, -N(COR8)-, -N(CO2R9)-, -N(SO2R9)-, -CO-O-, -O-CO-, -CO-NR8-, -NR8-CO-, -NR8-CO2-, -NR8-CO-NH-, -NR8-SO2- or-NR8-C(=NH)-NH -, and Z2 represents-O-, -CO-, -C(OH)R8-, -C(=N-OR8)-, -S-, -SO-, -SO2-, -NR8-, -N(COR8)-, -N(CO2R9)-, -N(SO2R9)-, -CO-O-, -O-CO-, -CO-NR8-, -NR8-CO-, -NR8-CO2-, -NR8-CO-NH-, -NR8-C(=NH)-NH-, -NR8-SO2- or-SO2-NR8-. In the above formulas (CH2)mand (CH2)noptionally substituted by one or more (preferably 1-5, more preferably 1-3) substituents selected, for example, from halogen, optionally halogenated C1-4of alkyl and hydroxy, and when m or n is not less than 2, a subset-CH2CH2groups (CH2)mand (CH2)noptionally replaced by-CH=CH - or-C≡C-.

In the above formulas, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl, or R6and R7form a ring together with a nitrogen atom. In these formulas, in addition, R8represents a hydrogen atom or a C1-4alkyl, and R9represents a C1-4alkyl. When R6and R7form a ring together with the nitrogen atom, as a nitrogen-containing heterocyclic group which you can specify for example, a 3-8-membered (preferably 5-or 6-membered) saturated or unsaturated (preferably saturated) aliphatic heterocyclic group, such as azetidine, pyrrolidine, piperidinyl, homopiperazine, heptamethylnonane, morpholinyl, thiomorpholine, piperazinil, homopiperazine and the like, and the like.

As X2preferred is a single bond.

Preferred R4represents a hydrogen atom or a C1-8alkyl group, a C2-8alkenylphenol group, C6-18aryl group or heterocyclic group, each of which is optionally substituted. As the preferred “C6-18aryl group” for R4is phenyl. Preferred “heterocyclic group” for R4is the above “5-or 6-membered aromatic monocyclic heterocyclic group”, preferably furyl.

As the “optionally substituted group attached through a carbon atom or a sulfur atom,for R2you can specify C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, karbamoilnuyu group, C1-8alkylcarboxylic group, C1-8alkylsulfonyl group, C3-8cycloalkyl group, C6-18aryl group, a C6-18aryl-C1-4alkyl group, a C-18 arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, C6-18arylsulfonyl group, heterocyclic group, a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted.

“C1-8alkyl group”, “C2-8Alchemilla group”, “C2-8Alchemilla group”, “C1-8acylcarnitine group”, “C1-8alkylsulfonyl group”, “C3-8cycloalkyl group”, “C6-18aryl group”, “C6-18aryl-C1-4alkyl group”, “C6-18arylcarbamoyl group”, “C6-18aryl-C1-4acylcarnitine group”, “C6-18arylsulfonyl group”, “heterocyclic group”, “heterocycle-C1-4alkyl group”, “getrollbackonly group” and “heterocycle-C1-4acylcarnitine group optionally substituted, for example, one or more (preferably 1-5, more preferably 1-3) substituents selected from the above group T substituents.

Preferred R2represents a hydrogen atom or a C1-8alkyl group, a C6-18aryl group, a C6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-18arylsulfonyl group or a heterocycle-C1-4 alkyl group, each of which is optionally substituted.

As “C6-18aryl group” for R2preferred is phenyl. As “C6-18aryl-C1-4alkyl group” for R2preferred is benzyl. As “C6-18arylcarboxylic group” for R2preferred is benzoyl. As “C6-18arylsulfonyl group” for R2it is preferable phenylsulfonyl. As the "heterocyclic group” or “heterocycle-heterocycle-C1-4alkyl group”, “heterocyclimamines group” and “heterocycle-C1-4alkylcarboxylic group” for R2preferred is the above “5-or 6-membered aromatic monocyclic heterocyclic group” or the above “aliphatic heterocyclic group”, preferably furyl or tetrahydrofuryl.

In the substituents, which the group represented by R2may contain, when R6and R7form a ring together with the nitrogen atom, the ring also contains optional 1-5 (preferably 1-3) are the same or different substituents. As such substituents can be specified substituents, such specified as examples of the “aryl group” or “heterocyclic group” for b

Above is carnemolla group” and “raidgroup” optionally contain 1 or 2 optionally substituted C 1-8alkyl groups. Alternatively, “carnemolla group” and “raidgroup” may contain two deputies and they may form, together with the adjacent nitrogen atom, optionally substituted ring. As a “ring” of the “optionally substituted ring”, you can specify a ring similar to those of the form R6and R7together with the nitrogen atom and which are given as examples above. As the “substituent” mentioned “optionally substituted C1-8alkyl group” as the “substituent” of the “optionally substituted ring”, you can specify groups similar to the substituents specified group T substituents.

As the “optionally substituted carbamoyl group, you can specify carbarnoyl, C1-8allylcarbamate, di(C1-8alkyl)carbarnoyl, C6-18aryl-C1-4allylcarbamate, azetidin-1-ylcarbonyl, pyrrolidin-1-ylcarbonyl, piperidine-1-ylcarbonyl, piperazine-1-ylcarbonyl, morpholine-4-ylcarbonyl, thiomorpholine-4-ylcarbonyl, (C1-4alkyl)piperidine-1-ylcarbonyl, (C6-18aryl-C1-4alkyl)piperidine-1-ylcarbonyl and the like.

As the “optionally substituted raidgroup” you can specify ureido, 3-(C1-8alkyl)ureido, 3,3-di(C1-8alkyl)ureido,

3-(C6-18aryl-C1-4alkyl)ureido, azetidin-1 ylcarbonyl,

pyrrolidin is-1 ylcarbonyl, piperidine-1-ylcarbonyl,

piperazine-1-ylcarbonyl, morpholine-4-ylcarbonyl,

thiomorpholine-4-ylcarbonyl,

(C1-4alkyl)piperidine-1-ylcarbonyl,

(C6-18aryl-C1-4alkyl)piperidine-1-ylcarbonyl and the like.

As the “ring structure” optionally substituted ring structure represented by the group R3associated with the carbon atom or a heteroatom in the aryl or heteroaryl group, And presents, you can specify a saturated or unsaturated (preferably saturated) 4-8-membered (preferably 5 - or 6-membered) nitrogen-containing heterocycle. In particular,represents

“The ring structure may contain 1-5 (preferably 1-3, more preferably 1 or 2 same or different substituents at any substitutable position(s). As such substituents can be specified substituents, such specified as examples of the “aryl group” or “heterocyclic group” for b

As the “ring structure” optionally substituted ring structure formed by groups of R1and R2associated with each other, you can specify a saturated or unsaturated (preferably saturated) 4-8-membered (preferably 5 - or 6-membered) GE is erotic. When R1and R2related to education optionally substituted ring structure, you can specify, for example,

wherein each symbol is as defined above, and the like.

As the “ring structure” optionally substituted ring structure formed by groups of R2and R3associated with each other, you can specify a saturated or unsaturated (preferably saturated) 4-8-membered (preferably 5 - or 7-membered) heterocycle. When R2and R3related to education optionally substituted ring structure, you can specify, for example,

wherein each symbol is as defined above, and the like. “Ring structure”formed by groups of R1and R2or R2and R3associated with each other, can contain 1-5 (preferably 1-3, more preferably 1 or 2 same or different substituents selected from the above group T substituents at any substitutable position(s).

When W represents C(R1), the compound (I) represented by the following formula (IA):

wherein each symbol is as defined above.

When W represents N, the compound (I) represented by the following formula the (IB) or (IC):

wherein each symbol is as defined above.

In particular, in the case of compound (I), preferably using the following compounds (Ia)to(Ij) and the like.

[Compound (Ia)]

The compound represented by the formula:

where R1arepresents a hydrogen atom or an optionally substituted group attached through a carbon atom, a nitrogen atom or an oxygen atom, and

R2ais an optionally substituted group attached through a carbon atom or a sulfur atom, or

R1aand R2aor R2aand R3anot necessarily related to education optionally substituted ring structure,

R3arepresents a hydrogen atom or optionally substituted aliphatic hydrocarbon group, or R3anot necessarily linked to the carbon atom of the adjacent phenyl group with the formation of optionally substituted ring structure,

Barepresents an optionally substituted benzene ring, and Carepresents an optionally substituted C6-18aryl group or its salt.

As the “optionally substituted group attached through a carbon atom, a nitrogen atom or an oxygen atom”for R1ayou can use groups like “obazatelno substituted group, attached via a carbon atom, a nitrogen atom or an oxygen atom”for R1.

As the “optionally substituted group attached through a carbon atom or a sulfur atom,for R2ayou can use group similar to the “optionally substituted group attached through a carbon atom or a sulfur atom”, for R2.

As the “optionally substituted ring structure”formed by groups of R1aand R2aor R2aand R3aassociated with each other, you can use patterns similar to the “optionally substituted ring structure”formed by groups of R1and R2or R2and R3associated with each other.

As the “optionally substituted aliphatic hydrocarbon group” for R3ayou can use group similar to the “optionally substituted aliphatic hydrocarbon group” for R3.

As the “optionally substituted ring structure” for R3awhich is formed by linking the carbon atoms adjacent phenyl group, you can use patterns similar to the “optionally substituted ring structure” for R3which is formed by linking the carbon atoms adjacent phenyl group.

As the substituent of the “optionally substituted benzene ring” is La B ayou can use, for example, 1 to 5 same or different substituents selected from halogen, optionally halogenated C1-4of alkyl, hydroxy, optionally halogenated1-4alkyloxy, C1-4allyloxymethyl, hydroxy-C1-4of alkyl, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonamides.

As “C6-18aryl group” of the “optionally substituted C6-18aryl group” for Cayou can use, for example, phenyl, biphenylyl, naphthyl, antril, tenantry, acenaphthylene and the like, preferably phenyl group.

As the “substituent” of the “optionally substituted C6-18aryl group” for Candyou can use the substituents, such substituents of the “optionally substituted benzene ring” for Ba.

Preferred R2arepresents a C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, karbamoilnuyu group, C1-8alkylcarboxylic group, C1-8alkylsulfonyl group, C3-8cycloalkyl group, C6-18aryl group, a C6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl groups who, C6-18aryl-C1-4alkylcarboxylic group, C6-18arylsulfonyl group, heterocyclic group, a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted by 1-5 substituents selected from the

(a) halogen,

(b) oxo,

(c) optionally halogenated C1-4of alkyl,

(d) -(CH2)m-Q,

(e) -(CH2)m-Z1-(optionally halogenated C1-4the alkyl),

(f) -(CH2)m-Z1-C3-8cycloalkyl,

(g) -(CH2)m-Z2-(CH2)n-Q,

(h) -(CH2)m-Z2-(CH2)n-Z1-(optionally halogenated C1-4the alkyl),

(i) -(CH2)m-Z2-(CH2)n-Z1-C3-8cycloalkyl,

(j) -(CH2)m-Z1-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom),

(k) -(CH2)m-Z2-C1-4alkoxy and

(l) -(CH2)m-Z2-(CH2)n-Z1-(CH2)n-Z1-C1-4the alkyl

where m is an integer from 0 is about 4, n is an integer from 1 to 4

Q represents hydroxy, carboxy, cyano, nitro, -NR6R7, -CONR6R7, -OCONH2or-SO2NR6R7,

Z1 represents-O-, -CO-, -C(OH)R8-, -C(=N-OR8)-, -S-, -SO-, -SO2-, -N(COR8)-, -N(CO2R9)-, -N(SO2R9)-, -CO-O-, -O-CO-, -CO-NR8-, -NR8-CO-, -NR8-CO2-, -NR8-CO-NH-, -NR8-SO2- or-NR8-C(=NH)-NH-,

Z2 represents-O-, -CO-, -C(OH)R8-, -C(=N-OR8)-, -S-, -SO-, -SO2-, -NR8-, -N(COR8)-, -N(CO2R9)-, -N(SO2R9)-, -CO-O-, -O-CO-, -CO-NR8-, -NR8-CO-, -NR8-CO2-, -NR8-CO-NH-, -NR8-C(=NH)-NH-, -NR8-SO2- or-SO2-NR8-,

(CH2)mand (CH2)noptionally substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4of alkyl and hydroxy, and when m or n is not less than 2, a subset-CH2CH2groups (CH2)mand (CH2)noptionally replaced by-CH=CH - or-C≡C-,

R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, or R6and R7related to education, together with the nitrogen atom, a 3-8-membered saturated or unsaturated aliphatic heterocyclic group,

R8represents and what Ohm hydrogen or C 1-4alkyl, and R9represents a C1-4alkyl.

As compound (Ia) is preferred connection, where

Barepresents a benzene ring, optionally substituted by 1-4 substituents selected from halogen, C1-4of alkyl, hydroxy-C1-4the alkyl and C1-4alkyloxy;

Carepresents a phenyl group, optionally substituted by 1-5 substituents selected from (i) halogen, (ii) optionally halogenated C1-4of alkyl, (iii) hydroxy-C1-4of alkyl, (iv) heterocycle-C1-4the alkyl (preferably 5-8-membered heterocycle-C1-4of alkyl, where the specified 5-8-membered heterocycle contains 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, such as imidazolyl, triazolyl and the like), (v) optionally halogenated C1-4alkyloxy, (vi) C1-4alkylsulphonyl, (vii) cyano, (viii) carbamoyl, optionally substituted C1-8of alkyl and (ix) C1-4alkoxycarbonyl;

R1arepresents a

(i) a hydrogen atom,

(ii) a cyano or

(iii) C1-4alkyl group or a C2-4alkenylphenol group, each of which is optionally substituted by-NR8-CO-(CH2)n-NR6R7where n is an integer from 1 to 4, R6and R7are the same or different and is jdy represents a hydrogen atom or a C 1-4alkyl group, R8represents a hydrogen atom or a C1-4alkyl group, and when n is not less than 2, a subset-CH2CH2group (CH2)noptionally replaced by-CH=CH-;

R2arepresents a C1-8alkyl group, a C2-8alkenylphenol group or a C2-8alkylamino group, each of which is optionally substituted by substituent(s)selected(s)

(a) hydroxy,

(b) carboxy,

(c) cyano,

(d) optionally halogenated C1-4alkyloxy,

(e) -O-(CH2)n-OH,

(f) -O-(CH2)n-O-CO-NH2,

(g) -O-(CH2)n-O-(optionally halogenated C1-4the alkyl),

(h) -O-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(i) -O-(CH2)n-SO2-C6-18aryl,

(j) -O-(CH2)n-SO2-(CH2)n-OH,

(k) -O-(CH2)n-NR8-CO-C1-4of alkyl,

(l) -O-(CH2)n-NR8-CO-(CH2)n-SO2-C1-4of alkyl,

(m) -O-(CH2)n-NR8-SO2-(optionally halogenated C1-4the alkyl),

(n) -CO-NR8-(CH2)n-OH,

(o) -CO-NR8-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(p) -CO-NR8-O-C1-4of alkyl,

(q) -NR6R7,

(r) -NR8-(CH2 n-OH,

(s) -NR8-(CH2)n-SO2-C1-4of alkyl,

(t) -NR8-CO-(optionally halogenated C1-4the alkyl),

(u) -NR8-CO-(CH2)n-OH,

(v) -NR8-CO-(CH2)n-CN

(w) -NR8-CO-(CH2)n-NR6R7,

(x) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(y) -NR8-CO-(CH2)n-SO-(optionally halogenated C1-4the alkyl),

(z) -NR8-CO-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(aa) -NR8-CO-(CH2)n-SO2-C3-8cycloalkyl,

(bb) -NR8-CO-(CH2)n-NR8-SO2-C1-4of alkyl,

(cc) -NR8-CO2-(CH2)n-SO2-C1-4of alkyl,

(dd) -NR8-CO-NH-(CH2)n-SO2-C1-4of alkyl,

(ee) -NR8-CO-NH-O-C1-4of alkyl,

(ff) -NR8-CO-NH-(CH2)n-O-C1-4of alkyl,

(gg) -NR8-C(=NH)-NH-C1-4of alkyl,

(hh) -NR8-SO2-(CH2)n-SO2-C1-4of alkyl,

(ii) -S-(CH2)n-OH,

(jj) -SO-(CH2)n-OH,

(kk) -SO2-(CH2)n-OH, and

(ll) -NR8-CO-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from at the mA nitrogen, oxygen atom and an optionally oxidized sulfur atom, which is optionally substituted by substituent(s)selected(s) hydroxy, C1-4the alkyl, optionally oxidized C1-4alkylthio, -CO-C1-4of alkyl, -CO-O-C1-4of alkyl, -CO-NH-C1-4of alkyl, -CONH2, -SO2-C1-4of alkyl, -SO2-NH-C1-4of alkyl, -SO2NH2and the like),

where n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, R8represents a hydrogen atom or a C1-4alkyl group, a group (CH2)noptionally substituted by optionally halogenated C1-4the alkyl or hydroxy, and when n is not less than 2, a subset-CH2CH2group (CH2)noptionally replaced by-CH=CH-; and

R3arepresents a hydrogen atom or a C1-6alkyl group; or

R1aand R2anot necessarily related to educationor; or

R2aand R3anot necessarily related to the formation of C2-4alkylene, optionally substituted aminogroups.

As R8preferred are a hydrogen atom, methyl, ethyl and the like, especially preferred is a hydrogen atom.

the as R 2apreferred is C1-8alkyl group, a C2-8Alchemilla group or C2-8Alchemilla group, each of which is optionally substituted by substituent(s)selected(s)

(a) hydroxy,

(b) carboxy,

(c) cyano,

(d) optionally halogenated C1-4alkyloxy,

(e) -O-(CH2)n-OH (where the group (CH2)noptionally substituted by hydroxy),

(f) -O-(CH2)n-O-CO-NH2,

(g) -O-(CH2)n-O-(optionally halogenated C1-4the alkyl),

(h) -O-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(i) -O-(CH2)n-SO2-C6-18aryl,

(j) -O-(CH2)n-SO2-(CH2)n-OH,

(k) -O-(CH2)n-NR8-CO-C1-4of alkyl,

(l) -O-(CH2)n-NR8-CO-(CH2)n-SO2-C1-4of alkyl,

(m) -O-(CH2)n-NR8-SO2-(optionally halogenated C1-4the alkyl),

(n) -CO-NR8-(CH2)n-OH,

(o) -CO-NR8-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(p) -CO-NR8-O-C1-4of alkyl,

(q) -NR6R7,

(r) -NR8-(CH2)n-OH,

(s) -NR8-(CH2)n-SO2-C1-4of alkyl,

(t) -NR8-CO-(optionally halogenated C1-4the alkyl),

(u-NR 8-CO-(CH2)n-OH (where the group (CH2)noptionally substituted by optionally halogenated C1-4the alkyl or hydroxy),

(v) -NR8-CO-(CH2)n-CN

(w) -NR8-CO-(CH2)n-NR6R7(when n is not less than 2, a subset-CH2CH2group (CH2)noptionally replaced by-CH=CH-),

(x) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(y) -NR8-CO-(CH2)n-SO-(optionally halogenated C1-4the alkyl),

(z) -NR8-CO-(CH2)n-SO2-(optionally halogenated C1-4the alkyl) (where the group (CH2)noptionally substituted C1-4by alkyl),

(aa) -NR8-CO-(CH2)n-SO2-C3-8cycloalkyl,

(bb) -NR8-CO-(CH2)n-NR8-SO2-C1-4of alkyl,

(cc) -NR8-CO2-(CH2)n-SO2-C1-4of alkyl,

(dd) -NR8-CO-NH-(CH2)n-SO2-C1-4of alkyl,

(ee) -NR8-CO-NH-O-C1-4of alkyl,

(ff) -NR8-CO-NH-(CH2)n-O-C1-4of alkyl,

(gg) -NR8-C(=NH)-NH-C1-4of alkyl,

(hh) -NR8-SO2-(CH2)n-SO2-C1-4of alkyl,

(ii) -S-(CH2)n-OH,

(jj) -SO-(CH2)n-OH,

(kk) -SO2-(CH2)n-OH, and

(ll) -NR8-CO-(optionally substituted heterocyclic group) (asanna heterocyclic group preferably is a 5-8-membered heterocyclic group, containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, which is optionally substituted by substituent(s)selected(s) hydroxy, C1-4the alkyl, optionally oxidized C1-4alkylthio, -CO-C1-4of alkyl, -CO-O-C1-4of alkyl, -CO-NH-C1-4of alkyl, -CONH2, -SO2-C1-4of alkyl, -SO2-NH-C1-4of alkyl, -SO2NH2and the like),

where n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, and R8represents a hydrogen atom or a C1-4alkyl group.

As R8preferred are a hydrogen atom, methyl, ethyl and the like, especially preferred is a hydrogen atom.

As compounds (Ia) are preferred is also a compound, where

Barepresents a benzene ring, optionally substituted by 1-4 substituents selected from halogen and optionally halogenated C1-4of alkyl;

Carepresents a phenyl group substituted by 1-5 substituents selected from (i) halogen, (ii) optionally halogenated C1-4of alkyl, (iii) hydroxy-C1-4of alkyl, (iv) heterocycle-C1-4the alkyl (preferably 5-8-membered heterocycle-C 1-4of alkyl, where the specified 5-8-membered heterocycle contains 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, such as imidazolyl and the like), (v) optionally halogenated C1-4alkyloxy, (vi) cyano, and (vii) of carbamoyl, optionally substituted C1-8by alkyl;

R1arepresents a hydrogen atom;

R2arepresents a C1-8alkyl group, a C2-8alkenylphenol group or a C2-8alkylamino group, each of which is substituted by substituent(s)selected(s)

(a) hydroxy,

(b) optionally halogenated C1-4alkyloxy,

(c) -O-(CH2)n-OH,

(d) -O-(CH2)n-O-CO-NH2,

(e) -O-(CH2)n-O-C1-4of alkyl,

(f) -O-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(g) -O-(CH2)n-SO2-C6-18aryl,

(h) -O-(CH2)n-SO2-(CH2)n-OH,

(i) -O-(CH2)n-NR8-SO2-(optionally halogenated C1-4the alkyl),

(j) -CO-NR8-(CH2)n-OH,

(k) -CO-NR8-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(l) -NR6R7,

(m) -NR8-(CH2)n-OH,

(n) -NR8-(CH2)n-SO2-C1-4of alkyl,

(o) -NR8-CO-(C 2)n-OH,

(p) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(q) -NR8-CO-(CH2)n-SO-(optionally halogenated C1-4the alkyl),

(r) -NR8-CO-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(s) -NR8-CO-(CH2)n-SO2-C3-8cycloalkyl,

(t) -NR8-CO2-(CH2)n-SO2-C1-4of alkyl,

(u) -NR8-CO-NH-(CH2)n-SO2-C1-4of alkyl,

(v) -NR8-SO2-(CH2)n-SO2-C1-4of alkyl,

(w) -S-(CH2)n-OH,

(x) -SO-(CH2)n-OH,

(y) -SO2-(CH2)n-OH, and

(z) -NR8-CO-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, which is optionally substituted by substituent(s)selected(s) hydroxy, C1-4the alkyl, optionally oxidized C1-4alkylthio, -CO-C1-4of alkyl, -CO-NH-C1-4of alkyl, -CONH2, -SO2-C1-4of alkyl, -SO2-NH-C1-4of alkyl, -SO2NH2and the like),

where n is an integer from 1 to 4, R6and R7are the same or different and each represents the Wallpaper atom of hydrogen or C 1-4alkyl group, R8represents a hydrogen atom or a C1-4alkyl group and the group (CH2)noptionally substituted C1-4the alkyl or hydroxy;

R3arepresents a hydrogen atom or a C1-6alkyl group; or

R1aand R2anot necessarily related to educationor; or

R2aand R3anot necessarily related to the formation of C2-4alkylene.

As described preferred R2arepresents a C1-8alkyl group, a C2-8alkenylphenol group or a C2-8alkylamino group (in particular, C1-8alkyl group), each of which is substituted by substituent(s)selected(s)

(a) hydroxy,

(b) optionally halogenated C1-4alkyloxy,

(c) -O-(CH2)n-OH (where the group (CH2)noptionally substituted by hydroxy),

(d) -O-(CH2)n-O-CO-NH2,

(e) -O-(CH2)n-O-C1-4of alkyl,

(f) -O-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(g) -O-(CH2)n-SO2-C6-18aryl,

(h) -O-(CH2)n-SO2-(CH2)n-OH,

(i) -O-(CH2)n-NR8-SO2-(optionally halogenated C1-4the alkyl),

(j) -CO-NR8-(CH2)n-OH,

(k) -CO-NR 8-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(l) -NR6R7,

(m) -NR8-(CH2)n-OH,

(n) -NR8-(CH2)n-SO2-C1-4of alkyl,

(o) -NR8-CO-(CH2)n-OH (where the group (CH2)noptionally substituted C1-4by alkyl),

(p) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(q) -NR8-CO-(CH2)n-SO-(optionally halogenated C1-4the alkyl),

(r) -NR8-CO-(CH2)n-SO2-(optionally halogenated C1-4the alkyl) (where the group (CH2)noptionally substituted C1-4by alkyl),

(s) -NR8-CO-(CH2)n-SO2-C3-8cycloalkyl,

(t) -NR8-CO2-(CH2)n-SO2-C1-4of alkyl,

(u) -NR8-CO-NH-(CH2)n-SO2-C1-4of alkyl,

(v) -NR8-SO2-(CH2)n-SO2-C1-4of alkyl,

(w) -S-(CH2)n-OH,

(x) -SO-(CH2)n-OH,

(y) -SO2-(CH2)n-OH, and

(z) -NR8-CO-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, which optionally C is mesena substituent(s), selected(I) from hydroxy, C1-4the alkyl, optionally oxidized C1-4alkylthio, -CO-C1-4of alkyl, -CO-NH-C1-4of alkyl, -CONH2, -SO2-C1-4of alkyl, -SO2-NH-C1-4of alkyl, -SO2NH2and the like),

where n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, R8represents a hydrogen atom or a C1-4alkyl group.

Preferred R2arepresents a

(i) C5-8alkyl group, a substituted hydroxy,

(ii) C1-8alkyl group substituted by substituent(s)selected(s)

(a) halogenated C1-4alkyloxy,

(b) -O-(CH2)n-OH,

(c) -O-(CH2)n-O-CO-NH2,

(d) -O-(CH2)n-O-(optionally halogenated C1-4the alkyl),

(e) -O-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(f) -O-(CH2)n-SO2-C6-18aryl,

(g) -O-(CH2)n-NR8-SO2-(optionally halogenated C1-4the alkyl),

(h) -CO-NR8-(CH2)n-OH,

(i) -CO-NR8-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(j) -NR8-(CH2)n-SO2-C1-4of alkyl,

(k) -NR8-CO-(CH2) n-OH,

(l) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(m) -NR8-CO-(CH2)n-SO-(optionally halogenated C1-4the alkyl),

(n) -NR8-CO-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(o) -NR8-CO-(CH2)n-SO2-C3-8cycloalkyl,

(p) -NR8-CO2-(CH2)n-SO2-C1-4of alkyl,

(q) -NR8-CO-NH-(CH2)n-SO2-C1-4of alkyl,

(r) -NR8-SO2-(CH2)n-SO2-C1-4of alkyl,

(s) -S-(CH2)n-OH,

(t) -SO-(CH2)n-OH,

(u) -SO2-(CH2)n-OH, and

(v) -NR8-CO-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, which is optionally substituted by substituent(s)selected(s) hydroxy, C1-4the alkyl, optionally oxidized C1-4alkylthio, -CO-C1-4of alkyl, -CO-NH-C1-4of alkyl, -CONH2, -SO2-C1-4of alkyl, -SO2-NH-C1-4of alkyl, -SO2NH2and the like),

where n is an integer from 1 to 4, R8represents a hydrogen atom or a C1-4alkyl group and the group (CH )noptionally substituted C1-4the alkyl or hydroxy,

(iii) C2-8alkenylphenol group, optionally substituted hydroxy, or

(iv) C2-8alkylamino group, optionally substituted hydroxy, and

particularly preferred R2arepresents a

(i) C5-8alkyl group, a substituted hydroxy,

(ii) C1-8alkyl group substituted by substituent(s)selected(s)

(a) halogenated C1-4alkyloxy,

(b) -O-(CH2)n-OH (where the group (CH2)noptionally substituted by hydroxy),

(c) -O-(CH2)n-O-CO-NH2,

(d) -O-(CH2)n-O-(optionally halogenated C1-4the alkyl),

(e) -O-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(f) -O-(CH2)n-SO2-C6-18aryl,

(g) -O-(CH2)n-NR8-SO2-(optionally halogenated C1-4the alkyl),

(h) -CO-NR8-(CH2)n-OH,

(i) -CO-NR8-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(j) -NR8-(CH2)n-SO2-C1-4of alkyl,

(k) -NR8-CO-(CH2)n-OH (where (CH2)noptionally substituted C1-4the alkyl),

(l) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(m) -NR8-CO-(CH2)n-SO-(optionally halo is enrevanche C 1-4the alkyl),

(n) -NR8-CO-(CH2)n-SO2-(optionally halogenated C1-4the alkyl) (where (CH2)noptionally substituted C1-4the alkyl),

(o) -NR8-CO-(CH2)n-SO2-C3-8cycloalkyl,

(p) -NR8-CO2-(CH2)n-SO2-C1-4of alkyl,

(q) -NR8-CO-NH-(CH2)n-SO2-C1-4of alkyl,

(r) -NR8-SO2-(CH2)n-SO2-C1-4of alkyl,

(s) -S-(CH2)n-OH,

(t) -SO-(CH2)n-OH,

(u) -SO2-(CH2)n-OH, and

(v) -NR8-CO-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, which is optionally substituted by substituent(s)selected(s) hydroxy, C1-4the alkyl, optionally oxidized C1-4alkylthio, -CO-C1-4of alkyl, -CO-NH-C1-4of alkyl, -CONH2, -SO2-C1-4of alkyl, -SO2-NH-C1-4of alkyl, -SO2NH2and the like),

where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group,

(iii) C2-8alkenylphenol group, optionally substituted hydroxy, or

(iv) C alkylamino group, optionally substituted hydroxy, and

as R8preferred are a hydrogen atom, methyl, ethyl and the like, especially preferred is a hydrogen atom.

[Compound (Ib)]

The compound represented by the formula:

where R1brepresents a hydrogen atom or an optionally substituted group attached through a carbon atom, a nitrogen atom or an oxygen atom

R2bis an optionally substituted group attached through a carbon atom or a sulfur atom, or

R1band R2bor R2band R3bnot necessarily related to education optionally substituted ring structure,

R3brepresents a hydrogen atom or optionally substituted aliphatic hydrocarbon group, or R3bnot necessarily linked to the carbon atom of the adjacent phenyl group with the formation of optionally substituted ring structure,

Bbrepresents an optionally substituted benzene ring, Cbrepresents an optionally substituted C6-18aryl group,

Zbrepresents an optionally substituted C1-3alkylenes group or its salt.

As the “optionally substituted group attached through an atom of plastics technology : turning & the Yes, a nitrogen atom or an oxygen atom”for R1byou can use group similar to the “optionally substituted group attached through a carbon atom, a nitrogen atom or an oxygen atom”for R1.

As the “optionally substituted group attached through a carbon atom or a sulfur atom,for R2byou can use group similar to the “optionally substituted group attached through a carbon atom or a sulfur atom”, for R2.

As the “optionally substituted ring structure”formed by groups of R1band R2bor R2band R3bassociated with each other, you can use patterns similar to the “optionally substituted ring structure”formed by groups of R1and R2or R2and R3associated with each other.

As the “optionally substituted aliphatic hydrocarbon group” for R3byou can use group similar to the “optionally substituted aliphatic hydrocarbon group” for R3.

As the “optionally substituted ring structure”formed by a group of R3band the carbon atom of the adjacent phenyl group, you can use patterns similar to the “optionally substituted ring structure”formed by a group of R3and the carbon atom of the adjacent phenyl g is uppy.

As the “optionally substituted benzene ring” for Bbyou can use a ring that is similar to the “optionally substituted benzene ring” for Ba.

As the “optionally substituted C6-18aryl group” for Cbyou can use group similar to the “optionally substituted C6-18aryl group” for Ca.

As “C1-3alkalinous group” of “optionally substituted C1-3alkalinous group” for Zbyou can use methylene, ethylene, trimethylene and propylene.

As the “substituent” of the “optionally substituted C1-3alkalinous group” for Zbyou can use 1-3 substituent selected from halogen, hydroxy, C1-4alkyloxy, C1-4alkylsulphonyl, carboxy, C1-4alkoxycarbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C1-4alkylcarboxylic, C1-4alkoxycarbonyl and C1-4alkylsulfonamides.

Preferred R2brepresents a C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, karbamoilnuyu group, C1-8alkylcarboxylic group, C1-8alkylsulfonyl group, C3-8cycloalkyl group, C6-18aryl group, a C6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-8 aryl-C1-4alkylcarboxylic group, C6-18arylsulfonyl group, heterocyclic group, a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted by 1-5 substituents selected from the

(a) halogen,

(b) oxo,

(c) optionally halogenated C1-4of alkyl,

(d) -(CH2)m-Q,

(e) -(CH2)m-Z1-(optionally halogenated C1-4the alkyl),

(f) -(CH2)m-Z1-C3-8cycloalkyl,

(g) -(CH2)m-Z2-(CH2)n-Q,

(h) -(CH2)m-Z2-(CH2)n-Z1-(optionally halogenated C1-4the alkyl),

(i) -(CH2)m-Z2-(CH2)n-Z1-C3-8cycloalkyl,

(j) -(CH2)m-Z1-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom),

(k) -(CH2)m-Z2-C1-4alkoxy and

(l) -(CH2)m-Z2-(CH2)n-Z1-(CH2)n-Z1-C1-4of alkyl,

where m is an integer from 0 to 4, n Rawa is an integer from 1 to 4

Q represents hydroxy, carboxy, cyano, nitro, -NR6R7, -CONR6R7, -OCONH2or-SO2NR6R7,

Z1 represents-O-, -CO-, -C(OH)R8-, -C(=N-OR8)-, -S-, -SO-, -SO2-, -N(COR8)-, -N(CO2R9)-, -N(SO2R9)-, -CO-O-, -O-CO-, -CO-NR8-, -NR8-CO-, -NR8-CO2-, -NR8-CO-NH-, -NR8-SO2- or-NR8-C(=NH)-NH-,

Z2 represents-O-, -CO-, -C(OH)R8-, -C(=N-OR8)-, -S-, -SO-, -SO2-, -NR8-, -N(COR8)-, -N(CO2R9)-, -N(SO2R9)-, -CO-O-, -O-CO-, -CO-NR8-, -NR8-CO-, -NR8-CO2-, -NR8-CO-NH-, -NR8-C(=NH)-NH-, -NR8-SO2- or-SO2-NR8-,

(CH2)mand (CH2)noptionally substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4of alkyl and hydroxy, and when m or n is not less than 2, a subset-CH2CH2groups (CH2)mand (CH2)noptionally replaced by-CH=CH - or-C≡C-,

R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, or R6and R7related to education, together with the nitrogen atom, a 3-8-membered saturated or unsaturated aliphatic heterocyclic group,

R8represents a hydrogen atom or a C1-4Ala is l and R 9represents a C1-4alkyl.

As the compounds (Ib), preferred is a compound where

Bbrepresents a benzene ring, optionally substituted with halogen;

Cbrepresents a phenyl group, optionally substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4the alkyl and cyano;

R1brepresents a

(i) a hydrogen atom, or

(ii) C2-4alkenylphenol group, optionally substituted hydroxy;

R2brepresents a

(i) C1-8alkyl group optionally substituted by substituent(s)selected(s)

(a) halogen,

(b) hydroxy,

(c) C1-4alkyloxy,

(d) -O-(CH2)n-OH,

(e) -O-(CH2)n-O-C1-4of alkyl,

(f) -CO-NR8-(CH2)n-OH,

(g) -NR6R7and

(h) -NR8-(CH2)n-OH,

where n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, and R8represents a hydrogen atom or a C1-4alkyl group,

(ii) C6-18aryl-C1-4alkyl group optionally substituted by substituent(s)selected(s)

(a) C1-4the alkyl, optionally containing hydroxy,

(b) carboxy,

(c) C1-4 alkoxycarbonyl,

(d) 5-8-membered heterocultural containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, which optionally has substituent(s)selected(e) of hydroxy and C1-4of alkyl, and

(e) C1-4allylcarbamate, optionally containing substituent(s)selected(e) of hydroxy and carbamoyl,

(iii) C6-18arylcarbamoyl group, optionally substituted C1-4alkoxy,

(iv) C6-18arylsulfonyl group, optionally substituted C1-4alkoxy, or

(v) 5-8-membered heterocycle-C1-4alkyl group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, which is optionally substituted by substituent(s)selected(s)

(a) carboxy, and

(b) C1-4alkoxycarbonyl;

R3brepresents a hydrogen atom or a C1-6alkyl group; or

R2band R3bnot necessarily related to the formation of C2-4alkylene; and

Zbrepresents a C1-3alkylenes group.

As the compounds (Ib), preferred is the compound where

Bbrepresents a benzene ring, optionally substituted with halogen;

Cbrepresents a phenyl group, optionally substituted by 1-5 substituents selected from halogen and optional what about the halogenated C 1-4of alkyl;

R1brepresents a hydrogen atom;

R2brepresents a C1-8alkyl group optionally substituted by substituent(s)selected(s)

(a) hydroxy,

(b) -O-(CH2)n-OH,

(c) -O-(CH2)n-O-C1-4of alkyl,

(d) -CO-NR8-(CH2)n-OH,

(e) -NR6R7and

(f) -NR8-(CH2)n-OH,

where n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, and R8represents a hydrogen atom or a C1-4alkyl group;

R3brepresents a hydrogen atom or a C1-6alkyl group;

Zbrepresents a C1-3alkylenes group.

Particularly preferred compound (Ib) is a compound where

Bbrepresents a benzene ring, optionally substituted with halogen;

Cbrepresents a phenyl group, optionally substituted by 1-5 substituents selected from halogen and optionally halogenated C1-4of alkyl;

R1brepresents a hydrogen atom;

R2brepresents a C1-8alkyl group substituted by substituent(s)selected(s)

(a) -O-(CH2)n-OH,

(b) -O-(CH2)n-O-C1-4alkyl and

(c) -CO-NR8-(CH2)n-OH,

where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group;

R3brepresents a hydrogen atom or a C1-6alkyl group;

Zbrepresents a methylene group.

As R8preferred are a hydrogen atom, methyl, ethyl and the like, especially preferred is a hydrogen atom.

[Compound (Ic)]

The compound represented by the formula:

where R1crepresents a hydrogen atom or an optionally substituted group attached through a carbon atom, a nitrogen atom or an oxygen atom

R2cis an optionally substituted group attached through a carbon atom or a sulfur atom, or

R1cand R2cor R2cand R3cnot necessarily related to education optionally substituted ring structure,

R3crepresents a hydrogen atom or optionally substituted aliphatic hydrocarbon group, or R3cnot necessarily linked to the carbon atom of the adjacent phenyl group with the formation of optionally substituted ring structure,

Bcrepresents an optionally substituted benzene ring, Ccis an optional C is displaced heterocyclic group or its salt.

As the “optionally substituted group attached through a carbon atom, a nitrogen atom or an oxygen atom” for R1cyou can use group similar to the “optionally substituted group attached through a carbon atom, a nitrogen atom or an oxygen atom” for R1.

As the “optionally substituted group attached through a carbon atom or a sulfur atom,for R2cyou can use group similar to the “optionally substituted group attached through a carbon atom or a sulfur atom,for R2.

As the “optionally substituted ring structure”formed by groups of R1cand R2cor R2cand R3cassociated with each other, you can use patterns similar to the “optionally substituted ring structure”formed by groups of R1and R2or R2and R3associated with each other.

As the “optionally substituted aliphatic hydrocarbon group” for R3cyou can use group similar to the “optionally substituted aliphatic hydrocarbon group” for R3.

As the “optionally substituted ring structure”formed by a group of R3cand the carbon atom of the adjacent phenyl group, you can use patterns similar to the “optionally substituted calcev the th structure”, formed by a group of R3and the carbon atom of the adjacent phenyl group.

As the “optionally substituted benzene ring” for Bcyou can use a ring that is similar to the “optionally substituted benzene ring” for Ba.

As the “heterocyclic group” of the “optionally substituted heterocyclic group” for Ccyou can use the above “heterocyclic group”, especially preferably 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom. In particular, you can use 5 or 6-membered aromatic monocyclic heterocyclic groups such as furyl, thienyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolin, imidazolyl, pyrazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, furazane, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl and the like, 3-8-membered (preferably 5 - or 6-membered) saturated or unsaturated (preferably saturated) aliphatic heterocyclic groups, such as oxiranyl, azetidine, oxetane, titanyl, pyrrolidinyl, tetrahydrofuryl, tylenol, piperidyl, tetrahydropyranyl, Mor is oliner, thiomorpholine, piperazinil, dihydro-1,2,4-oxadiazolyl and the like, particularly preferably pyridyl, pyrimidinyl, piperidyl (in particular, 4-piperidyl) and the like.

As the “substituent” of the “optionally substituted heterocyclic group” for Ccyou can use substitutes such as “Deputy” of the “optionally substituted C6-18aryl group” for Ca.

Preferred R2crepresents a C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, karbamoilnuyu group, C1-8alkylcarboxylic group, C1-8alkylsulfonyl group, C3-8cycloalkyl group, C6-18aryl group, a C6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, C6-18arylsulfonyl group, heterocyclic group, a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted by 1-5 substituents selected from the

(a) halogen,

(b) oxo,

(c) optionally halogenated C1-4of alkyl,

(d) -(CH2)m-Q,

(e) -(CH2)m-Z1-(optionally halogenated C1-4the alkyl),

(f) -(CH2)m-Z1-C cycloalkyl,

(g) -(CH2)m-Z2-(CH2)n-Q,

(h) -(CH2)m-Z2-(CH2)n-Z1-(optionally halogenated C1-4the alkyl),

(i) -(CH2)m-Z2-(CH2)n-Z1-C3-8cycloalkyl,

(j) -(CH2)m-Z1-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom),

(k) -(CH2)m-Z2-C1-4alkoxy and

(l) -(CH2)m-Z2-(CH2)n-Z1-(CH2)n-Z1-C1-4of alkyl,

where m is an integer from 0 to 4, n is an integer from 1 to 4

Q represents hydroxy, carboxy, cyano, nitro, -NR6R7, -CONR6R7or-SO2NR6R7,

Z1 represents-O-, -CO-, -C(OH)R8-, -C(=N-OR8)-, -S-, -SO-, -SO2-, -N(COR)-, -N(CO2R9)-, -N(SO2R9)-, -CO-O-, -O-CO-, -CO-NR8-, -NR8-CO-, -NR8-CO2-, -NR8-CO-NH-, -NR8-SO2- or-NR8-C(=NH)-NH-,

Z2 represents-O-, -CO-, -C(OH)R8-, -C(=N-OR8)-, -S-, -SO-, -SO2-, -NR8-, -N(COR8)-, -N(CO2R9)-, -N(SO2R9)-, -CO-O-, -O-CO-, -CO-NR8 -, -NR8-CO-, -NR8-CO2-, -NR8-CO-NH-, -NR8-C(=NH)-NH-, -NR8-SO2- or-SO2-NR8-,

(CH2)mand (CH2)noptionally substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4of alkyl and hydroxy, and when m or n is not less than 2, a subset-CH2CH2groups (CH2)mand (CH2)noptionally replaced by-CH=CH-,

R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, or R6and R7related to education, together with the nitrogen atom, a 3-8-membered saturated or unsaturated aliphatic heterocyclic group,

R8represents a hydrogen atom or a C1-4alkyl, and R9represents a C1-4alkyl.

As compound (Ic) is the preferred connection, where

Bcrepresents a benzene ring, optionally substituted by 1-4 substituents selected from halogen and optionally halogenated C1-4of alkyl;

Ccis a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom (for example, pyridyl, pyrimidyl, 4-piperidyl), which is optionally substituted by 1-5 substituents selected is from

(i) halogen,

(ii) C1-4of alkyl,

(iii) C1-4alkylcarboxylic,

(iv) optionally halogenated C1-4alkoxycarbonyl,

(v) C3-8cycloalkylcarbonyl and

(vi) carbamoyl group, optionally substituted by substituent(s)selected(s)

(a) optionally halogenated C1-8of alkyl,

(b) C3-8cycloalkyl and

(c) C6-18aryl, optionally substituted by substituent(s)selected(s) halogen, C1-4the alkyl and C1-4alkyloxy;

R1crepresents a

(i) a hydrogen atom,

(ii) C2-4alkenylphenol group, optionally substituted hydroxy, or

(iii) 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom;

R2crepresents a

(i) C1-4alkyl group optionally substituted by substituent(s)selected(s)

(a) halogen,

(b) hydroxy,

(c) C1-4alkyloxy,

(d) carboxy,

(e) C1-4alkoxycarbonyl,

(f) -O-(CH2)n-OH,

(g) -O-(CH2)n-O-C1-4of alkyl,

(h) -CO-NR8-(CH2)n-OH, and

(i) -NR8-CO-(CH2)n-SO2-C1-4of alkyl,

where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group, or

(ii) C6-18aryl-C1-4alkyl is ing group, optionally substituted C1-4the alkyl, optionally containing hydroxy;

R3crepresents a hydrogen atom or a C1-6alkyl group; or

R2cand R3cnot necessarily related to the formation of C2-4alkylene.

As compound (Ic) is also preferred connection, where

Bcrepresents a benzene ring, optionally substituted by 1-4 substituents selected from halogen and C1-4of alkyl;

Ccis a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, which optionally is substituted by 1-5 substituents selected from the

(i) C1-4of alkyl,

(ii) C1-4alkylcarboxylic,

(iii) optionally halogenated C1-4alkoxycarbonyl,

(iv)C3-8cycloalkylcarbonyl and

(v) carbamoyl group, optionally substituted by substituent(s)selected(s)

(a) optionally halogenated C1-8of alkyl,

(b) C3-8cycloalkyl and

(c) C6-18aryl, optionally substituted with halogen;

R1crepresents a hydrogen atom;

R2crepresents a C1-4alkyl group optionally substituted by substituent(s)selected(s)

(a) hydroxy,

(b) C1-4alkyloxy,

(c) -O-(CH2) -OH,

(d) -O-(CH2)n-O-C1-4the alkyl and

(e) -NR8-CO-(CH2)n-SO2-C1-4of alkyl,

where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group;

R3crepresents a hydrogen atom or a C1-6alkyl group, particularly preferred is the compound where R2crepresents a C1-4alkyl group optionally substituted by substituent(s)selected(s)

(a) -O-(CH2)n-OH, and

(b) -O-(CH2)n-O-C1-4of alkyl,

where n is an integer from 1 to 4.

[Connection Id]

The compound represented by the formula

where R1drepresents a hydrogen atom or an optionally substituted group attached through a carbon atom, a nitrogen atom or an oxygen atom

R2dis an optionally substituted group attached through a carbon atom or a sulfur atom, or

R1dand R2dor R2dand R3dnot necessarily related to education optionally substituted ring structure,

R3drepresents a hydrogen atom or optionally substituted aliphatic hydrocarbon group, or R3dnot necessarily linked to the carbon atom of the adjacent phenyl group education is not necessary for esenkoy ring structure

Bdrepresents an optionally substituted benzene ring, Cdrepresents an optionally substituted heterocyclic group, and

Zdrepresents an optionally substituted C1-3alkylenes group or its salt.

As the “optionally substituted group attached through a carbon atom, a nitrogen atom or an oxygen atom” for R1dyou can use group similar to the “optionally substituted group attached through a carbon atom, a nitrogen atom or an oxygen atom” for R1.

As the “optionally substituted group attached through a carbon atom or a sulfur atom,for R2dyou can use group similar to the “optionally substituted group attached through a carbon atom or a sulfur atom”, for R2.

As the “optionally substituted ring structure”formed by groups of R1dand R2dor R2dand R3dassociated with each other, you can use patterns similar to the “optionally substituted ring structure”formed by groups of R1and R2or R2and R3associated with each other.

As the “optionally substituted aliphatic hydrocarbon group” for R3dyou can use group similar to the “optionally substituted aliphatic the coy hydrocarbon group” for R 3.

As the “optionally substituted ring structure”formed by a group of R3dand the carbon atom of the adjacent phenyl group, you can use patterns similar to the “optionally substituted ring structure”formed by a group of R3and the carbon atom of the adjacent phenyl group.

As the “optionally substituted benzene ring” for Bdyou can use a ring that is similar to the “optionally substituted benzene ring” for Ba.

As the “optionally substituted heterocyclic group” for Cdyou can use group similar to the “optionally substituted heterocyclic group” for Cc.

As the “optionally substituted C1-3alkalinous group” for Zdyou can use group similar to the “optionally substituted C1-3alkalinous group” for Zb.

Preferred R2drepresents a C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, karbamoilnuyu group, C1-8alkylcarboxylic group, C1-8alkylsulfonyl group, C3-8cycloalkyl group, C6-18aryl group, a C6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, C6-18and ylsulphonyl group, heterocyclic group, a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted by 1-5 substituents selected from the

(a) halogen,

(b) oxo,

(c) optionally halogenated C1-4of alkyl,

(d) -(CH2)m-Q,

(e) -(CH2)m-Z1-(optionally halogenated C1-4the alkyl),

(f) -(CH2)m-Z1-C3-8cycloalkyl,

(g) -(CH2)m-Z2-(CH2)n-Q,

(h) -(CH2)m-Z2-(CH2)n-Z1-(optionally halogenated C1-4the alkyl),

(i) -(CH2)m-Z2-(CH2)n-Z1-C3-8cycloalkyl,

(j) -(CH2)m-Z1-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom),

(k) -(CH2)m-Z2-C1-4alkoxy and

(l) -(CH2)m-Z2-(CH2)n-Z1-(CH2)n-Z1-C1-4of alkyl,

where m is an integer from 0 to 4, n is an integer from 1 to 4

Q represents hydroxy, carboxy, cyano, NIT is about, -NR6R7, -CONR6R7or-SO2NR6R7,

Z1 represents-O-, -CO-, -C(OH)R8-, -C(=N-OR8)-, -S-, -SO-, -SO2-, -N(COR8)-, -N(CO2R9)-, -N(SO2R9)-, -CO-O-, -O-CO-, -CO-NR8-, -NR8-CO-, -NR8-CO2-, -NR8-CO-NH-, -NR8-SO2- or-NR8-C(=NH)-NH-,

Z2 represents-O-, -CO-, -C(OH)R8-, -C(=N-OR8)-, -S-, -SO-, -SO2-, -NR8-, -N(COR8)-, -N(CO2R9)-, -N(SO2R9)-, -CO-O-, -O-CO-, -CO-NR8-, -NR8-CO-, -NR8-CO2-, -NR8-CO-NH-, -NR8-C(=NH)-NH-, -NR8-SO2- or-SO2-NR8-,

(CH2)mand (CH2)noptionally substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4of alkyl and hydroxy, and when m or n is not less than 2, a subset-CH2CH2groups (CH2)mand (CH2)noptionally replaced by-CH=CH-,

R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, or R6and R7related to education, together with the nitrogen atom, a 3-8-membered saturated or unsaturated aliphatic heterocyclic group,

R8represents a hydrogen atom or a C1-4alkyl, and R9represents a C1-4alkyl.

As the connection Id is preferred connection, where

Bdrepresents a benzene ring, optionally substituted with halogen;

Cdis a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom;

R1drepresents a hydrogen atom;

R2drepresents a

(i) C1-4alkyl, optionally substituted by substituent(s)selected(s)

(a) C1-4alkyloxy

(b) -O-(CH2)n-OH, and

(c) -NR8-CO-(CH2)n-SO2-C1-4of alkyl,

where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group, or

(ii) 5-8-membered heterocycle-C1-4alkyl group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, which is optionally substituted by substituent(s)selected(s)

(a) carboxy, and

(b) C1-4alkoxycarbonyl;

R3drepresents a hydrogen atom or a C1-6alkyl group;

Zdrepresents a C1-3alkylenes group.

As compound (Id) is also preferred connection, where

Bdrepresents a benzene ring, optionally substituted with halogen;

Cdis a 5-8-membered heterocyclic group containing 1-3 heteroatoms, wybran the x from a nitrogen atom, oxygen atom and sulfur atom;

R1drepresents a hydrogen atom,

R2drepresents a C1-4alkyl group, optionally substituted C1-4alkyloxy,

R3drepresents a hydrogen atom or a C1-6alkyl group;

Zdrepresents a methylene group.

[Compound (Ie)]

The compound represented by the formula:

where R2eis an optionally substituted group attached through a carbon atom or a sulfur atom, or

R2eand R3enot necessarily related to education optionally substituted ring structure,

R3erepresents a hydrogen atom or optionally substituted aliphatic hydrocarbon group, or R3enot necessarily linked to the carbon atom of the adjacent phenyl group with the formation of optionally substituted ring structure,

Berepresents an optionally substituted benzene ring, and Cerepresents an optionally substituted C6-18aryl group or its salt.

As the “optionally substituted group attached through a carbon atom or a sulfur atom,for R2eyou can use group similar to the “optionally substituted group attached through a carbon atom or atom CE is s”, for R2.

As the “optionally substituted ring structure”formed by groups of R2eand R3eassociated with each other, you can use patterns similar to the “optionally substituted ring structure”formed by groups of R2and R3associated with each other.

As the “optionally substituted aliphatic hydrocarbon group” for R3eyou can use group similar to the “optionally substituted aliphatic hydrocarbon group” for R3.

As the “optionally substituted ring structure”formed by a group of R3eand the carbon atom of the adjacent phenyl group, you can use patterns similar to the “optionally substituted ring structure”formed by a group of R3and the carbon atom of the adjacent phenyl group.

As the “optionally substituted benzene ring” for Beyou can use a ring that is similar to the “optionally substituted benzene ring” for Ba.

As the “optionally substituted C6-18aryl group” for Ceyou can use group similar to the “optionally substituted C6-18aryl group” for Ca.

Preferred R2erepresents a C1-8alkyl group, a C2-8alkenylphenol group, C28 alkylamino group, karbamoilnuyu group, C1-8alkylcarboxylic group, C1-8alkylsulfonyl group, C3-8cycloalkyl group, C6-18aryl group, a C6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, C6-18arylsulfonyl group, heterocyclic group, a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted by 1-5 substituents selected from the

(a) halogen,

(b) oxo,

(c) optionally halogenated C1-4of alkyl,

(d) -(CH2)m-Q,

(e) -(CH2)m-Z1-(optionally halogenated C1-4the alkyl),

(f) -(CH2)m-Z1-C3-8cycloalkyl,

(g) -(CH2)m-Z2-(CH2)n-Q,

(h) -(CH2)m-Z2-(CH2)n-Z1-optionally halogenated C1-4of alkyl,

(i) -(CH2)m-Z2-(CH2)n-Z1-C3-8cycloalkyl,

(j) -(CH2)m-Z1-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from an atom and the PTA, oxygen atom and an optionally oxidized sulfur atom),

(k) -(CH2)m-Z2-C1-4alkoxy and

(l) -(CH2)m-Z2-(CH2)n-Z1-(CH2)n-Z1-C1-4alkyl,

where m is an integer from 0 to 4, n is an integer from 1 to 4

Q represents hydroxy, carboxy, cyano, nitro, -NR6R7, -CONR6R7or-SO2NR6R7,

Z1 represents-O-, -CO-, -C(OH)R8-, -C(=N-OR8)-, -S-, -SO-, -SO2-, -N(COR8)-, -N(CO2R9)-, -N(SO2R9)-, -CO-O-, -O-CO-, -CO-NR8-, -NR8-CO-, -NR8-CO2-, -NR8-CO-NH-, -NR8-SO2- or-NR8-C(=NH)-NH-,

Z2 represents-O-, -CO-, -C(OH)R8-, -C(=N-OR8)-, -S-, -SO-, -SO2-, -NR8-, -N(COR8)-, -N(CO2R9)-, -N(SO2R9)-, -CO-O-, -O-CO-, -CO-NR8-, -NR8-CO-, -NR8-CO2-, -NR8-CO-NH-, -NR8-C(=NH)-NH-, -NR8-SO2- or-SO2-NR8-,

(CH2)mand (CH2)noptionally substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4of alkyl and hydroxy, and when m or n is not less than 2, a subset-CH2CH2groups (CH2)mand (CH2)noptionally replaced by-CH=CH-,

R6and R7are the same or different and each represents sobo is a hydrogen atom or a C 1-4alkyl group, or R6and R7related to education, together with the nitrogen atom, a 3-8-membered saturated or unsaturated aliphatic heterocyclic group,

R8represents a hydrogen atom or a C1-4alkyl, and R9represents a C1-4alkyl.

As compound (Ie) is the preferred connection, where

Berepresents a benzene ring, optionally substituted with halogen;

Cerepresents a phenyl group optionally substituted by optionally halogenated C1-4by alkyl; and

R2erepresents a C1-4alkyl group, optionally substituted-O-(CH2)n-OH, where n is an integer from 1 to 4.

As compound (Ie) is also preferred connection, where

Berepresents a benzene ring, optionally substituted with halogen;

Cerepresents a phenyl group optionally substituted by optionally halogenated C1-4by alkyl;

R2erepresents a C1-4alkyl group, substituted-O-(CH2)n-OH, where n is an integer from 1 to 4.

[Compound (If)]

The compound represented by the formula:

where R2fis an optionally substituted group, connected iannou through a carbon atom or a sulfur atom; or

R2fand R3fnot necessarily related to education optionally substituted ring structure,

R3frepresents a hydrogen atom or optionally substituted aliphatic hydrocarbon group, or R3fnot necessarily linked to the carbon atom of the adjacent phenyl group with the formation of optionally substituted ring structure,

Bfrepresents an optionally substituted benzene ring, Cfrepresents an optionally substituted C6-18aryl group,

Zfrepresents an optionally substituted C1-3alkylenes group or its salt.

As the “optionally substituted group attached through a carbon atom or a sulfur atom,for R2fyou can use group similar to the “optionally substituted group attached through a carbon atom or a sulfur atom”, for R2.

As the “optionally substituted ring structure”formed by groups of R2fand R3fassociated with each other, you can use patterns similar to the “optionally substituted ring structure”formed by groups of R2and R3associated with each other.

As the “optionally substituted aliphatic hydrocarbon group” for R3fyou can use group similar to the“optionally substituted aliphatic hydrocarbon group” for R 3.

As the “optionally substituted ring structure”formed by a group of R3fand the carbon atom of the adjacent phenyl group, you can use patterns similar to the “optionally substituted ring structure”formed by a group of R3and the carbon atom of the adjacent phenyl group.

As the “optionally substituted benzene ring” for Bfyou can use a ring that is similar to the “optionally substituted benzene ring” for Ba.

As the “optionally substituted C6-18aryl group” for Cfyou can use group similar to the “optionally substituted C6-18aryl group” for Ca.

As the “optionally substituted C1-3alkalinous group” for Zfyou can use group similar to the “optionally substituted C1-3alkalinous group” for Zb.

Preferred R2frepresents a C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, karbamoilnuyu group, C1-8alkylcarboxylic group, C1-8alkylsulfonyl group, C3-8cycloalkyl group, C6-18aryl group, a C6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, C6-18and ylsulphonyl group, heterocyclic group, a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted by 1-5 substituents selected from the

(a) halogen,

(b) oxo,

(c) optionally halogenated C1-4of alkyl,

(d) -(CH2)m-Q,

(e) -(CH2)m-Z1-(optionally halogenated C1-4the alkyl),

(f) -(CH2)m-Z1-C3-8cycloalkyl,

(g) -(CH2)m-Z2-(CH2)n-Q,

(h) -(CH2)m-Z2-(CH2)n-Z1-optionally halogenated C1-4of alkyl,

(i) -(CH2)m-Z2-(CH2)n-Z1-C3-8cycloalkyl,

(j) -(CH2)m-Z1-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom),

(k) -(CH2)m-Z2-C1-4alkoxy and

(l) -(CH2)m-Z2-(CH2)n-Z1-(CH2)n-Z1-C1-4of alkyl,

where m is an integer from 0 to 4, n is an integer from 1 to 4

Q represents hydroxy, carboxy, cyano, NITR is, -NR6R7, -CONR6R7or-SO2NR6R7,

Z1 represents-O-, -CO-, -C(OH)R8-, -C(=N-OR8)-, -S-, -SO-, -SO2-, -N(COR8)-, -N(CO2R9)-, -N(SO2R9)-, -CO-O-, -O-CO-, -CO-NR8-, -NR8-CO-, -NR8-CO2-, -NR8-CO-NH-, -NR8-SO2- or-NR8-C(=NH)-NH-,

Z2 represents-O-, -CO-, -C(OH)R8-, -C(=N-OR8)-, -S-, -SO-, -SO2-, -NR8-, -N(COR8)-, -N(CO2R9)-, -N(SO2R9)-, -CO-O-, -O-CO-, -CO-NR8-, -NR8-CO-, -NR8-CO2-, -NR8-CO-NH-, -NR8-C(=NH)-NH-, -NR8-SO2- or-SO2-NR8-,

(CH2)mand (CH2)noptionally substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4of alkyl and hydroxy, and when m or n is not less than 2, a subset-CH2CH2groups (CH2)mand (CH2)noptionally replaced by-CH=CH-,

R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, or R6and R7related to education, together with the nitrogen atom, a 3-8-membered saturated or unsaturated aliphatic heterocyclic group,

R8represents a hydrogen atom or a C1-4alkyl, and R9represents a C1-4alkyl.

The quality of the connection (If preferred is a compound where

Bfrepresents a benzene ring, optionally substituted with halogen;

Cfrepresents a phenyl group, optionally substituted with halogen;

R2frepresents a

(i) C1-4alkyl group, optionally substituted by 1-5 substituents selected from the group consisting of

(a) hydroxy,

(b) -O-(CH2)n-OH,

(c) -NR8-(CH2)n-O-C1-4of alkyl,

(d) -NR8-(CH2)n-heterocyclic group (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom),

(e) -NR8-(CH2)n-SO2-C1-4of alkyl,

where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group,

(ii) C6-18aryl group, optionally substituted by 1-5 substituents selected from the group consisting of

(a) C1-4the alkyl, optionally substituted by substituent(s)selected(s) hydroxy, -NR8-(CH2)n-OH, -NR8-(CH2)n-O-C1-4of alkyl, -NR8-(CH2)n-heterocyclic group (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1 to heteroatom, selected from nitrogen atom, oxygen atom and sulfur atom) and-NR8-(CH2)n-SO2-C1-4of alkyl, and

(b) -CO-NR8-(CH2)n-O-C1-4of alkyl,

where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group, or

(iii) C6-18aryl-C1-4alkyl group, optionally substituted by 1-5 substituents selected from the group consisting of

(a) carboxy,

(b) C1-4alkoxycarbonyl and

(c) -CO-NR8-(CH2)n-O-C1-4of alkyl, where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group,

R3frepresents a hydrogen atom or a C1-6alkyl group; and

Zfrepresents a C1-3alkylenes group; or

R2fand R3fnot necessarily related to the formation of C2-4alkylene.

As R8preferred are a hydrogen atom, methyl, ethyl and the like, especially preferred is a hydrogen atom.

As the compound (If) is also preferred connection, where

Bfrepresents a benzene ring, optionally substituted with halogen;

Cfrepresents a phenyl group, optionally substituted with halogen;

R2frepresents a C1-4the alkyl group is from, optionally substituted by 1-5 substituents selected from the group consisting of

(a) hydroxy, and

(b) -O-(CH2)n-OH, where n is an integer from 1 to 4;

R3frepresents a hydrogen atom or a C1-6alkyl group;

Zfrepresents a methylene, especially preferred is the compound where R2frepresents a C1-4alkyl group, substituted-O-(CH2)n-OH, where n is an integer from 1 to 4.

[Connect Ig)]

The compound represented by the formula:

where R2gis an optionally substituted group attached through a carbon atom or a sulfur atom, or

R2gand R3gnot necessarily related to education optionally substituted ring structure,

R3grepresents a hydrogen atom or optionally substituted aliphatic hydrocarbon group, or R3gnot necessarily linked to the carbon atom of the adjacent phenyl group with the formation of optionally substituted ring structure,

Bgrepresents an optionally substituted benzene ring, and Cgrepresents an optionally substituted heterocyclic group, or its salt.

As the “optionally substituted group attached through a carbon atom or a sulfur atom” for R 2gyou can use group similar to the “optionally substituted group attached through a carbon atom or a sulfur atom,for R2.

As the “optionally substituted ring structure”formed by groups of R2gand R3gassociated with each other, you can use patterns similar to the “optionally substituted ring structure”formed by groups of R2and R3associated with each other.

As the “optionally substituted aliphatic hydrocarbon group” for R3gyou can use group similar to the “optionally substituted aliphatic hydrocarbon group” for R3.

As the “optionally substituted ring structure”formed by a group of R3gand the carbon atom of the adjacent phenyl group, you can use patterns similar to the “optionally substituted ring structure”formed by a group of R3and the carbon atom of the adjacent phenyl group.

As the “optionally substituted benzene ring” for Bgyou can use a ring that is similar to the “optionally substituted benzene ring” for Ba.

As the “optionally substituted heterocyclic group” for Cgyou can use group similar to the “optionally substituted heterocyclic group is e for C c.

Preferred R2grepresents a C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, karbamoilnuyu group, C1-8alkylcarboxylic group, C1-8alkylsulfonyl group, C3-8cycloalkyl group, C6-18aryl group, a C6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, C6-18arylsulfonyl group, heterocyclic group, a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted by 1-5 substituents selected from the

(a) halogen,

(b) oxo,

(c) optionally halogenated C1-4of alkyl,

(d) -(CH2)m-Q,

(e) -(CH2)m-Z1-(optionally halogenated C1-4the alkyl),

(f) -(CH2)m-Z1-C3-8cycloalkyl,

(g) -(CH2)m-Z2-(CH2)n-Q,

(h) -(CH2)m-Z2-(CH2)n-Z1-(optionally halogenated C1-4the alkyl),

(i) -(CH2)m-Z2-(CH2)n-Z1-C3-8cycloalkyl,

(j) -(CH2)m-Z1-(optionally substituted heterocyclic group) (this heterocyclic group is and preferably represents a 5-8-membered heterocyclic group, containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom),

(k) -(CH2)m-Z2-C1-4alkoxy and

(l) -(CH2)m-Z2-(CH2)n-Z1-(CH2)n-Z1-C1-4of alkyl,

where m is an integer from 0 to 4, n is an integer from 1 to 4

Q represents hydroxy, carboxy, cyano, nitro, -NR6R7, -CONR6R7or-SO2NR6R7,

Z1 represents-O-, -CO-, -C(OH)R8-, -C(=N-OR8)-, -S-, -SO-, -SO2-, -N(COR8)-, -N(CO2R9)-, -N(SO2R9)-, -CO-O-, -O-CO-, -CO-NR8-, -NR8-CO-, -NR8-CO2-, -NR8-CO-NH-, -NR8-SO2- or-NR8-C(=NH)-NH-,

Z2 represents-O-, -CO-, -C(OH)R8-, -C(=N-OR8)-, -S-, -SO-, -SO2-, -NR8-, -N(COR8)-, -N(CO2R9)-, -N(SO2R9)-, -CO-O-, -O-CO-, -CO-NR8-, -NR8-CO-, -NR8-CO2-, -NR8-CO-NH-, -NR8-C(=NH)-NH-, -NR8-SO2- or-SO2-NR8-,

(CH2)mand (CH2)noptionally substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4of alkyl and hydroxy, and when m or n is not less than 2, a subset-CH2CH2groups (CH2)mand (CH2)noptionally replaced by-CH=CH-,

R6and R7are about incopyme or different and each represents a hydrogen atom or a C 1-4alkyl group, or R6and R7related to education, together with the nitrogen atom, a 3-8-membered saturated or unsaturated aliphatic heterocyclic group,

R8represents a hydrogen atom or a C1-4alkyl, and R9represents a C1-4alkyl.

As the compounds (Ig), preferred is a compound where

Bgrepresents a benzene ring, optionally substituted C1-4by alkyl;

Cgis a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, which is optionally substituted C1-4by alkyl;

R2grepresents a

(i) C1-4alkyl group, optionally substituted hydroxy,

(ii) C6-18aryl group optionally substituted by substituent(s)selected(s)

(a) nitro,

(b) amino,

(c) -CO-NR8-(CH2)n-O-C1-4of alkyl,

(d) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(e) -NR8-CO-(CH2)n-NR6R7,

(f) -NR8-CO-(CH2)n-COOH,

(g) -NR8-CO-(CH2)n-CO2-C1-4the alkyl and

(h) -NR8-CO-(CH2)m-O-(CH2)n-O-C1-4of alkyl,

where m is an integer from 0 to 4, n is an integer from 1 to 4, R6and R7aglautdinova or different and each represents a hydrogen atom or a C 1-4alkyl group, and R8represents a hydrogen atom or a C1-4alkyl group, or

(iii) C6-18aryl-C1-4alkyl group optionally substituted by substituent(s)selected(s)

(a) carboxy,

(b) C1-4alkoxycarbonyl and

(c) -CO-NR8-(CH2)n-O-C1-4of alkyl, where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group;

R3grepresents a hydrogen atom or a C1-6alkyl group; or

R2gand R3gnot necessarily related to the formation of C2-4alkylen.

As the compounds (Ig), preferred is a compound where

R2grepresents a

(i) C6-18aryl group optionally substituted by substituent(s)selected(s)

(a) nitro,

(b) amino,

(c) -CO-NR8-(CH2)n-O-C1-4of alkyl,

(d) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(e) -NR8-CO-(CH2)n-NR6R7,

(f) -NR8-CO-(CH2)n-COOH,

(g) -NR8-CO-(CH2)n-CO2-C1-4the alkyl and

(h) -NR8-CO-(CH2)m-O-(CH2)n-O-C1-4of alkyl,

where m is an integer from 0 to 4, n is an integer from 1 to 4, R6and R7are the same or different and each represents an atom of water is kind or C 1-4alkyl group, and R8represents a hydrogen atom or a C1-4alkyl group, or

(ii) C6-18aryl-C1-4alkyl group substituted by substituent(s)selected(s)

(a) carboxy,

(b) C1-4alkoxycarbonyl and

(c) -CO-NR8-(CH2)n-O-C1-4of alkyl, where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group.

As R8preferred are a hydrogen atom, methyl, ethyl and the like, especially preferred is a hydrogen atom.

[Compound (Ih)]

The compound (I)selected from the following (a)-(H).

(A) compound (I), where W represents CR1;

A represents phenyloxy-C6-18aryl group, where

phenyloxy-part optionally substituted by 1-5 substituents selected from the

(i) halogen,

(ii) optionally halogenated C1-4of alkyl,

(iii) hydroxy-C1-4of alkyl,

(iv) heterocycle-C1-4the alkyl (preferably 5-8-membered heterocycle-C1-4of alkyl, where the specified 5-8-membered heterocycle contains 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, such as imidazolyl, triazolyl and the like),

(v) optionally halogenated C1-4alkyloxy,

(vi) C1-4alkyls is bonila,

(vii) cyano,

(viii) carbamoyl, optionally substituted C1-8the alkyl, and

(ix) C1-4alkoxycarbonyl, and

C6-18the aryl part is optionally substituted by 1-4 substituents selected from halogen, C1-4of alkyl, hydroxy-C1-4of alkyl, C1-4alkyloxy, carboxy and C1-4alkoxycarbonyl;

X1 represents-NR3'-where R3'represents a hydrogen atom or a C1-6alkyl group;

R1represents a

(i) a hydrogen atom,

(ii) a cyano or

(iii) C1-4alkyl group or a C2-4alkenylphenol group, each of which is optionally substituted by-NR8-CO-(CH2)n-NR6R7where n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, R8represents a hydrogen atom or a C1-4alkyl group, and when n is not less than 2, a subset-CH2CH2group (CH2)noptionally replaced by-CH=CH-;

R2represents a

(i) a hydrogen atom, or

(ii) C1-8alkyl group, a C2-8alkenylphenol group or a C2-8alkylamino group, each of which is optionally substituted by substituent(s)selected(s)

(a) hydroxy,

(b) carboxy,

(c) cyano,

(d) long is Ino halogenated C 1-4alkyloxy,

(e) -O-(CH2)n-OH,

(f) -O-(CH2)n-O-CO-NH2,

(g) -O-(CH2)n-O-(optionally halogenated C1-4the alkyl),

(h) -O-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(i) -O-(CH2)n-SO2-C6-18aryl,

(j) -O-(CH2)n-SO2-(CH2)n-OH,

(k) -O-(CH2)n-NR8-CO-C1-4of alkyl,

(l) -O-(CH2)n-NR8-CO-(CH2)n-SO2-C1-4of alkyl,

(m) -O-(CH2)n-NR8-SO2-(optionally halogenated C1-4the alkyl),

(n) -CO-NR8-(CH2)n-OH,

(o) -CO-NR8-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(p) -CO-NR8-O-C1-4of alkyl,

(q) -NR6R7,

(r) -NR8-(CH2)n-OH,

(s) -NR8-(CH2)n-SO2-C1-4of alkyl,

(t) -NR8-CO-(optionally halogenated C1-4the alkyl),

(u) -NR8-CO-(CH2)n-OH,

(v) -NR8-CO-(CH2)n-CN

(w) -NR8-CO-(CH2)n-NR6R7,

(x) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(y) -NR8-CO-(CH2)n-SO-(optionally halogenated C1-4the alkyl),

(z) -NR8-CO-(CH2)n-SO2-(optionally halogenated C1-4 the alkyl),

(aa) -NR8-CO-(CH2)n-SO2-C3-8cycloalkyl,

(bb) -NR8-CO-(CH2)n-NR8-SO2-C1-4of alkyl,

(cc) -NR8-CO2-(CH2)n-SO2-C1-4of alkyl,

(dd) -NR8-CO-NH-(CH2)n-SO2-C1-4of alkyl,

(ee) -NR8-CO-NH-O-C1-4of alkyl,

(ff) -NR8-CO-NH-(CH2)n-O-C1-4of alkyl,

(gg) -NR8-C(=NH)-NH-C1-4of alkyl,

(hh) -NR8-SO2-(CH2)n-SO2-C1-4of alkyl,

(ii) -S-(CH2)n-OH,

(jj) -SO-(CH2)n-OH,

(kk) -SO2-(CH2)n-OH, and

(ll) -NR8-CO-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, which is optionally substituted by substituent(s)selected(s) hydroxy, C1-4the alkyl, optionally oxidized C1-4alkylthio, -CO-C1-4of alkyl, -CO-O-C1-4of alkyl, -CO-NH-C1-4of alkyl, -CONH2, -SO2-C1-4of alkyl, -SO2-NH-C1-4of alkyl, -SO2NH2and the like),

where n is an integer from 1 to 4, R6and R7are the same or different and each represents an atom bodoro is a or C 1-4alkyl group, R8represents a hydrogen atom or a C1-4alkyl group, a group (CH2)noptionally substituted by optionally halogenated C1-4the alkyl or hydroxy, and when n is not less than 2, a subset-CH2CH2group (CH2)noptionally replaced by-CH=CH-; or

R1and R2not necessarily related to education; or

R2and R3'not necessarily related to the formation of C2-4alkylene, optionally substituted aminogroups,

particularly preferably, R2arepresents a C1-8alkyl group, a C2-8alkenylphenol group or a C2-8alkylamino group (in particular, C1-8alkyl group), each of which is optionally substituted by substituent(s)selected(s)

(a) hydroxy,

(b) carboxy,

(c) cyano,

(d) optionally halogenated C1-4alkyloxy,

(e) -O-(CH2)n-OH (where the group (CH2)noptionally substituted by hydroxy),

(f) -O-(CH2)n-O-CO-NH2,

(g) -O-(CH2)n-O-(optionally halogenated C1-4the alkyl),

(h) -O-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(i) -O-(CH2)n-SO2-C6-18aryl,

(j) -O-(CH2)n-SO2-(CH2) n-OH,

(k) -O-(CH2)n-NR8-CO-C1-4of alkyl,

(l) -O-(CH2)n-NR8-CO-(CH2)n-SO2-C1-4of alkyl,

(m) -O-(CH2)n-NR8-SO2-(optionally halogenated C1-4the alkyl),

(n) -CO-NR8-(CH2)n-OH,

(o) -CO-NR8-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(p) -CO-NR8-O-C1-4of alkyl,

(q) -NR6R7,

(r) -NR8-(CH2)n-OH,

(s) -NR8-(CH2)n-SO2-C1-4of alkyl,

(t) -NR8-CO-(optionally halogenated C1-4the alkyl),

(u) -NR8-CO-(CH2)n-OH (where the group (CH2)noptionally substituted by optionally halogenated C1-4the alkyl or hydroxy),

(v) -NR8-CO-(CH2)n-CN

(w) -NR8-CO-(CH2)n-NR6R7(when n is not less than 2, a subset-CH2CH2group (CH2)noptionally replaced by-CH=CH-),

(x) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(y) -NR8-CO-(CH2)n-SO-(optionally halogenated C1-4the alkyl),

(z) -NR8-CO-(CH2)n-SO2-(optionally halogenated C1-4the alkyl) (where the group (CH2)noptionally substituted C1-4by alkyl),

(aa) -NR8-CO-(CH2)nSO 2-C3-8cycloalkyl,

(bb) -NR8-CO-(CH2)n-NR8-SO2-C1-4of alkyl,

(cc) -NR8-CO2-(CH2)n-SO2-C1-4of alkyl,

(dd) -NR8-CO-NH-(CH2)n-SO2-C1-4of alkyl,

(ee) -NR8-CO-NH-O-C1-4of alkyl,

(ff) -NR8-CO-NH-(CH2)n-O-C1-4of alkyl,

(gg) -NR8-C(=NH)-NH-C1-4of alkyl,

(hh) -NR8-SO2-(CH2)n-SO2-C1-4of alkyl,

(ii) -S-(CH2)n-OH,

(jj) -SO-(CH2)n-OH,

(kk) -SO2-(CH2)n-OH, and

(ll) -NR8-CO-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, which is optionally substituted by substituent(s)selected(s) hydroxy, C1-4the alkyl, optionally oxidized C1-4alkylthio, -CO-C1-4of alkyl, -CO-O-C1-4of alkyl, -CO-NH-C1-4of alkyl, -CONH2, -SO2-C1-4of alkyl, -SO2-NH-C1-4of alkyl, -SO2NH2and the like),

where n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, and R8depict is to place an atom of hydrogen or C 1-4alkyl group.

(B) compound (I), where W represents CR1;

A represents a phenyl-C1-3alkyloxy-C6-18aryl group, where the phenyl portion optionally substituted by 1-5 substituents selected from halogen, optionally halogenated C1-4the alkyl and cyano, and

C6-18the aryl part is optionally substituted by 1-4 substituents selected from halogen, C1-4the alkyl, optionally containing hydroxy, and C1-4alkyloxy;

X1 represents-NR3'-where R3'represents a hydrogen atom or a C1-6alkyl group;

R1represents a

(i) a hydrogen atom, or

(ii) C1-4alkyl group or a C2-4alkenylphenol group, each of which is optionally substituted by substituent(s)selected(s)

(a) hydroxy,

(b) amino and

(c) -NR8-CO-(CH2)n-NR6R7where n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, and R8represents a hydrogen atom or a C1-4alkyl group,

(iii) C6-18aryl group optionally substituted by substituent(s)selected(s)

(a) amino,

(b) carboxy,

(c) -NR8-CO-(CH2)n-O-C1-4the alkyl and

(d) -NR8 2)n-O-C1-4of alkyl,

where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group, and when n is not less than 2, a subset-CH2-CH2group (CH2)noptionally replaced by-CH=CH-, or

(iv) 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom;

R2represents a

(i) a hydrogen atom,

(ii) C1-8alkyl group optionally substituted by substituent(s)selected(s)

(a) halogen,

(b) hydroxy,

(c) C1-4alkyloxy,

(d) -O-(CH2)n-OH,

(e) -O-(CH2)n-O-C1-4of alkyl,

(f) -CO-NR8-(CH2)n-OH,

(g) -NR6R7and

(h) -NR8-(CH2)n-OH,

where n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, and R8represents a hydrogen atom or a C1-4alkyl group,

(iii) C6-18aryl-C1-4alkyl group optionally substituted by substituent(s)selected(s)

(a) C1-4the alkyl, optionally containing hydroxy,

(b) carboxy,

(c) C1-4alkoxycarbonyl,

(d) 5-8-membered heterocultural containing 1-3 heteroatoms selected from and what Ohm nitrogen, oxygen atom and sulfur atom, which optionally has substituent(s)selected(e) of hydroxy and C1-4of alkyl, and

(e) C1-4allylcarbamate, optionally containing substituent(s)selected(e) of hydroxy and carbamoyl,

(iv) C6-18arylcarbamoyl group, optionally substituted C1-4alkoxy,

(v) C6-18arylsulfonyl group, optionally substituted C1-4alkoxy, or

(vi) 5-8-membered heterocycle-C1-4alkyl group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, which is optionally substituted by substituent(s)selected(s)

(a) carboxy, and

(b) C1-4alkoxycarbonyl; or

R2and R3'not necessarily related to the formation of C2-4alkylene.

(C) compound (I), where W represents CR1;

And is a 5-8-membered, heterocyclic-C6-18aryl group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, where heterocyclics-part optionally substituted by 1-5 substituents selected from the

(i) halogen,

(ii) C1-4of alkyl,

(iii) C1-4alkylcarboxylic,

(iv) optionally halogenated C1-4alkoxycarbonyl,

(v) C3-8cycloalkylcarbonyl and

(vi) carbamoyl group, optionally substituted by substituent(s), you the screen(s)

(a) optionally halogenated C1-8of alkyl,

(b) C3-8cycloalkyl and

(c) C6-18aryl, optionally substituted by substituent(s)selected(s) halogen, C1-4the alkyl and C1-4alkyloxy, and

C6-18the aryl part is optionally substituted by 1-4 substituents selected from halogen and optionally halogenated C1-4of alkyl;

X1 represents-NR3'-where R3'represents a hydrogen atom or a C1-6alkyl group;

R1represents a

(i) a hydrogen atom,

(ii) C1-4alkyl group or a C2-4alkenylphenol group, each of which is optionally substituted by substituent(s)selected(s)

(a) hydroxy,

(b) amino,

(c) -NR8-CO-(CH2)n-NR6R7and

(d) -NR8-CO-(CH2)n-O-C1-4of alkyl,

where n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, R8represents a hydrogen atom or a C1-4alkyl group, and when n is not less than 2, a subset-CH2CH2group (CH2)noptionally replaced by-CH=CH-,

(iii) C6-18aryl group optionally substituted by substituent(s)selected(s)

(a) C1-4the alkyl, optional C is displaced by substituent(s), selected(I) from hydroxy, -NR8-(CH2)n-SO2-C1-4the alkyl and-NR8-CO-(CH2)n-O-C1-4of alkyl,

(b) amino,

(c) C1-4alkyloxy,

(d) carboxy, and

(e) -NR8-CO-(CH2)n-O-C1-4of alkyl,

where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group, or

(iv) 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom;

R2represents a

(i) a hydrogen atom,

(ii) C1-4alkyl group optionally substituted by substituent(s)selected(s)

(a) halogen,

(b) hydroxy,

(c) C1-4alkyloxy,

(d) carboxy,

(e) C1-4alkoxycarbonyl,

(f) -O-(CH2)n-OH,

(g) -O-(CH2)n-O-C1-4of alkyl,

(h) -CO-NR8-(CH2)n-OH, and

(i) -NR8-CO-(CH2)n-SO2-C1-4of alkyl,

where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group, or

(iii) C6-18aryl-C1-4alkyl group, optionally substituted C1-4the alkyl, optionally containing hydroxy; or

R2and R3'not necessarily related to the formation of C2-4alkylene.

(D) compound (I), where W represents CR1;

A performance is to place a 5-8-membered heterocycle-C 1-3alkyloxy-C6-18aryl group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom;

where C6-18the aryl part is optionally substituted with halogen;

X1 represents-NR3'-where R3'represents a hydrogen atom or a C1-6alkyl group;

R1represents a

(i) a hydrogen atom, or

(ii) 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom;

R2represents a

(i) a hydrogen atom,

(ii) C1-4alkyl, optionally substituted by substituent(s)selected(s)

(a) C1-4alkyloxy,

(b) -O-(CH2)n-OH, and

(c) -NR8-CO-(CH2)n-SO2-C1-4of alkyl,

where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group, or

(iii) 5-8-membered heterocycle-C1-4alkyl group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, which is optionally substituted by substituent(s)selected(s)

(a) carboxy, and

(b) C1-4alkoxycarbonyl.

(E) compound (I), where W represents N;

A represents phenyloxy-C6-18aryl group, where phenyloxy-part optionally substituted by 1-5 substituents selected from h is necessarily halogenated C 1-4the alkyl and cyano, and

C6-18the aryl part is optionally substituted by 1-4 substituents selected from halogen and C1-4of alkyl;

X1 represents-NR3'-where R3'represents a hydrogen atom or a C1-6alkyl group;

R2represents a

(i) a hydrogen atom, or

(ii) C1-4alkyl group, optionally substituted-O-(CH2)n-OH, where n is an integer from 1 to 4.

(F) compound (I), where W represents N;

A represents a phenyl-C1-3alkyloxy-C6-18aryl group, where the phenyl portion optionally substituted by 1-5 substituents selected from halogen and cyano, and

C6-18the aryl part is optionally substituted by 1-5 substituents selected from halogen and C1-4of alkyl;

X1 represents-NR3'-where R3'represents a hydrogen atom or a C1-6alkyl group;

R2represents a

(i) a hydrogen atom,

(ii) C1-4alkyl group, optionally substituted by 1-5 substituents selected from the group consisting of

(a) hydroxy,

(b) -O-(CH2)n-OH,

(c) -NR8-(CH2)n-O-C1-4of alkyl,

(d) -NR8-(CH2)n-heterocyclic group (this heterocyclic group preferably is a 5-8-membered heterocyclics the group, containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom), and

(e) -NR8-(CH2)n-SO2-C1-4of alkyl,

where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group,

(iii) C6-18aryl group, optionally substituted C1-4the alkyl, optionally substituted by substituent(s)selected(s) hydroxy, -NR8-(CH2)n-OH, -NR8-(CH2)n-heterocyclic group (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom) and-NR8-(CH2)n-SO2-C1-4the alkyl, or

(iv) C6-18aryl-C1-4alkyl group, optionally substituted by 1-5 substituents selected from the group consisting of

(a) carboxy,

(b) C1-4alkoxycarbonyl and

(c) -CO-NR8-(CH2)n-O-C1-4of alkyl, where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group; or

R2and R3'not necessarily related to the formation of C2-4alkylene.

(G) Compound (I), where W represents N;

And is a 5-8-membered, heterocyclic-C6-18aryl group containing 1-3 Goethe is the atom carrying, selected from nitrogen atom, oxygen atom and sulfur atom, where heterocyclics-part optionally substituted C1-4the alkyl, and

C6-18the aryl part is optionally substituted C1-4by alkyl;

X1 represents-NR3'-where R3'represents a hydrogen atom or a C1-6alkyl group;

R2represents a

(i) a hydrogen atom,

(ii) C1-4alkyl group, optionally substituted hydroxy,

(iii) C6-18aryl group optionally substituted by substituent(s)selected(s)

(a) nitro,

(b) amino,

(c) -CO-NR8-(CH2)n-O-C1-4of alkyl,

(d) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(e) -NR8-CO-(CH2)n-NR6R7,

(f) -NR8-CO-(CH2)n-COOH,

(g) -NR8-CO-(CH2)n-CO2-C1-4the alkyl and

(h) -NR8-CO-(CH2)m-O-(CH2)n-O-C1-4of alkyl,

where m is an integer from 0 to 4, n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, and R8represents a hydrogen atom or a C1-4alkyl group, or

(iv) C6-18aryl-C1-4alkyl group optionally substituted by substituent(s)selected(s)

(a) carboxy,

(b) C-4 alkoxycarbonyl and

(c) -CO-NR8-(CH2)n-O-C1-4of alkyl, where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group; and

R2and R3'not necessarily related to the formation of C2-4alkylene.

(H) compound (I), where W represents CH;

A represents a C6-18aryl group optionally substituted by substituent(s)selected(s)

(a) carboxy,

(b) C1-4alkoxycarbonyl,

(c) 5-8-membered heterocyclimamines group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom (preferably 5-8-membered cyclic aminocarbonyl group, optionally containing 1 or 2 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, which optionally substituted C6-18aryl-C1-4the alkyl,

(d) carbamoyl group, optionally substituted C6-18aryl-C1-4the alkyl, and

(e) raidgroup, optionally substituted C6-18aryl-C1-4by alkyl;

X1 represents-NR3'-where R3'represents a hydrogen atom or a C1-6alkyl group; and

R2represents a hydrogen atom.

[The compound (Ii)]

The compound (I), where a represents a C6-18aryl group substituted by substituent(s)selected(s)

(a) halogen,

(b) optionally halogenated C1-4of alkyl,

(c) hydroxy-C1-4of alkyl,

(d) heterocycle-C1-4the alkyl (preferably 5-8-membered heterocycle-C1-4of alkyl, where the specified 5-8-membered heterocycle contains 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, such as imidazolyl, triazolyl and the like),

(e) optionally halogenated C1-4alkyloxy,

(f) C1-4alkylcarboxylic,

(g) cyano,

(h) carbamoyl, optionally substituted C1-8the alkyl, and

(i) C1-4alkoxycarbonyl,

(ii) phenyl-C1-3alkyloxy, substituted by 1-5 substituents selected from the

(a) halogen,

(b) optionally halogenated C1-4of alkyl,

(c) hydroxy-C1-4of alkyl,

(d) heterocycle-C1-4the alkyl (preferably 5-8-membered heterocycle-C1-4of alkyl, where the specified 5-8-membered heterocycle contains 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, such as imidazolyl, triazolyl and the like),

(e) optionally halogenated C1-4alkyloxy,

(f) C1-4alkylcarboxylic,

(g) cyano,

(h) carbamoyl, optionally substituted C1-8the alkyl, and

(i) C1-4alkoxide is bonila,

(iii) 5-8-membered heterozygosity containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, which is substituted by 1-5 substituents selected from the

(a) halogen,

(b) optionally halogenated C1-4of alkyl,

(c) hydroxy-C1-4of alkyl,

(d) heterocycle-C1-4the alkyl (preferably 5-8-membered heterocycle-C1-4of alkyl, where the specified 5-8-membered heterocycle contains 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, such as imidazolyl, triazolyl and the like),

(e) optionally halogenated C1-4alkyloxy,

(f) C1-4alkylcarboxylic,

(g) cyano,

(h) carbamoyl, optionally substituted C1-8the alkyl, and

(i) C1-4alkoxycarbonyl, and

(iv) 5-8-membered heterocycle-C1-3alkyloxy containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, which is substituted by 1-5 substituents selected from the

(a) halogen,

(b) optionally halogenated C1-4of alkyl,

(c) hydroxy-C1-4of alkyl,

(d) heterocycle-C1-4the alkyl (preferably 5-8-membered heterocycle-C1-4of alkyl, where the specified 5-8-membered heterocycle contains 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, such as imidazole is, triazolyl and the like),

(e) optionally halogenated C1-4alkyloxy,

(f) C1-4alkylcarboxylic,

(g) cyano,

(h) carbamoyl, optionally substituted C1-8the alkyl, and

(i) C1-4alkoxycarbonyl;

where C6-18the aryl group optionally substituted by 1-4 substituents selected from halogen and optionally halogenated C1-4of alkyl;

R1represents a hydrogen atom;

R2represents a C1-8alkyl group, a C2-8alkenylphenol group or a C2-8alkylamino group, each of which is substituted by substituent(s)selected(s)

(a) hydroxy,

(b) carboxy,

(c) cyano,

(d) optionally halogenated C1-4alkyloxy,

(e) -O-(CH2)n-OH,

(f) -O-(CH2)n-O-CO-NH2,

(g) -O-(CH2)n-O-(optionally halogenated C1-4the alkyl),

(h) -O-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(i) -O-(CH2)n-SO2-C6-18aryl,

(j) -O-(CH2)n-SO2-(CH2)n-OH,

(k) -O-(CH2)n-NR8-CO-C1-4of alkyl,

(l) -O-(CH2)n-NR8-CO-(CH2)n-SO2-C1-4of alkyl,

(m) -O-(CH2)n-NR8-SO2-(optionally halogenated C1-4the alkyl),

(n) -CO-R 8-(CH2)n-OH,

(o) -CO-NR8-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(p) -CO-NR8-O-C1-4of alkyl,

(q) -NR6R7,

(r) -NR8-(CH2)n-OH,

(s) -NR8-(CH2)n-SO2-C1-4of alkyl,

(t) -NR8-CO-(optionally halogenated C1-4the alkyl),

(u) -NR8-CO-(CH2)n-OH,

(v) -NR8-CO-(CH2)n-CN

(w) -NR8-CO-(CH2)n-NR6R7,

(x) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(y) -NR8-CO-(CH2)n-SO-(optionally halogenated C1-4the alkyl),

(z) -NR8-CO-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(aa) -NR8-CO-(CH2)n-SO2-C3-8cycloalkyl,

(bb) -NR8-CO-(CH2)n-NR8-SO2-C1-4of alkyl,

(cc) -NR8-CO2-(CH2)n-SO2-C1-4of alkyl,

(dd) -NR8-CO-NH-(CH2)n-SO2-C1-4of alkyl,

(ee) -NR8-CO-NH-O-C1-4of alkyl,

(ff) -NR8-CO-NH-(CH2)n-O-C1-4of alkyl,

(gg) -NR8-C(=NH)-NH-C1-4of alkyl,

(hh) -NR8-SO2-(CH2)n-SO2-C1-4of alkyl,

(ii) -S-(CH2)n-OH,

(jj) -SO-(CH2)n-OH,

(kk) -SO2-(CH2)n-OH, and

(ll) -NR8/sup> -CO-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, which is optionally substituted by substituent(s)selected(s) hydroxy, C1-4the alkyl, optionally oxidized C1-4alkylthio, -CO-C1-4of alkyl, -CO-O-C1-4of alkyl, -CO-NH-C1-4of alkyl, -CONH2, -SO2-C1-4of alkyl, -SO2-NH-C1-4of alkyl, -SO2NH2and the like),

where n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, R8represents a hydrogen atom or a C1-4alkyl group, a group (CH2)noptionally substituted by optionally halogenated C1-4the alkyl or hydroxy, and when n is not less than 2, a subset-CH2CH2group (CH2)noptionally replaced by-CH=CH-;

R3represents a hydrogen atom or a C1-6alkyl group; or

R1and R2not necessarily related to educationor; or

R2and R3not necessarily related to obrazovaniem 2-4alkylene, optionally substituted aminogroups,

particularly preferably, R2represents a C1-8alkyl group, a C2-8alkenylphenol group or a C2-8alkylamino group (in particular, C1-8alkyl group), each of which is optionally substituted by substituent(s)selected(s)

(a) hydroxy,

(b) carboxy,

(c) cyano,

(d) optionally halogenated C1-4alkyloxy,

(e) -O-(CH2)n-OH (where the group (CH2)noptionally substituted by hydroxy),

(f) -O-(CH2)n-O-CO-NH2,

(g) -O-(CH2)n-O-(optionally halogenated C1-4the alkyl),

(h) -O-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(i) -O-(CH2)n-SO2-C6-18aryl,

(j) -O-(CH2)n-SO2-(CH2)n-OH,

(k) -O-(CH2)n-NR8-CO-C1-4of alkyl,

(l) -O-(CH2)n-NR8-CO-(CH2)n-SO2-C1-4of alkyl,

(m) -O-(CH2)n-NR8-SO2-(optionally halogenated C1-4the alkyl),

(n) -CO-NR8-(CH2)n-OH,

(o) -CO-NR8-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(p) -CO-NR8-O-C1-4of alkyl,

(q) -NR6R7,

(r) -NR8-(CH2)n-OH,

(s) -NR8 -(CH2)n-SO2-C1-4of alkyl,

(t) -NR8-CO-(optionally halogenated C1-4the alkyl),

(u) -NR8-CO-(CH2)n-OH (where the group (CH2)noptionally substituted by optionally halogenated C1-4the alkyl or hydroxy),

(v) -NR8-CO-(CH2)n-CN

(w) -NR8-CO-(CH2)n-NR6R7(when n is not less than 2, a subset-CH2CH2group (CH2)noptionally replaced by-CH=CH-),

(x) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(y) -NR8-CO-(CH2)n-SO-(optionally halogenated C1-4the alkyl),

(z) -NR8-CO-(CH2)n-SO2-(optionally halogenated C1-4the alkyl) (where the group (CH2)noptionally substituted C1-4by alkyl),

(aa) -NR8-CO-(CH2)n-SO2-C3-8cycloalkyl,

(bb) -NR8-CO-(CH2)n-NR8-SO2-C1-4of alkyl,

(cc) -NR8-CO2-(CH2)n-SO2-C1-4of alkyl,

(dd) -NR8-CO-NH-(CH2)n-SO2-C1-4of alkyl,

(ee) -NR8-CO-NH-O-C1-4of alkyl,

(ff) -NR8-CO-NH-(CH2)n-O-C1-4of alkyl,

(gg) -NR8-C(=NH)-NH-C1-4of alkyl,

(hh) -NR8-SO2-(CH2)n-SO2-C1-4of alkyl,

(ii) -S-(CH2)n-OH,

(jj) -SO-(CH2 )n-OH,

(kk) -SO2-(CH2)n-OH, and

(ll) -NR8-CO-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, which is optionally substituted by substituent(s)selected(s) hydroxy, C1-4the alkyl, optionally oxidized C1-4alkylthio, -CO-C1-4of alkyl, -CO-O-C1-4of alkyl, -CO-NH-C1-4of alkyl, -CONH2, -SO2-C1-4of alkyl, -SO2-NH-C1-4of alkyl, -SO2NH2and the like),

where n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, and R8represents a hydrogen atom or a C1-4alkyl group.

[Compound (Ij)]

The compound (I) where

A represents a C6-18aryl group substituted by substituent(s)selected(s)

(i) fenoxaprop, substituted by 1-5 substituents selected from the

(a) halogen,

(b) optionally halogenated C1-4of alkyl,

(c) hydroxy-C1-4of alkyl,

(d) heterocycle-C1-4the alkyl (preferably 5-8-membered heterocycle-C1-4of alkyl, where the specified 5-8-clenn the th heterocycle contains 1-3 heteroatoms, selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, such as imidazolyl and the like),

(e) optionally halogenated C1-4alkyloxy,

(f) cyano,

(g) carbamoyl, optionally substituted C1-8the alkyl, and

(h) C1-4alkoxycarbonyl,

(ii) phenyl-C1-3alkyloxy, substituted by 1-5 substituents selected from the

(a) halogen,

(b) optionally halogenated C1-4of alkyl,

(c) hydroxy-C1-4of alkyl,

(d) heterocycle-C1-4the alkyl (preferably 5-8-membered heterocycle-C1-4of alkyl, where the specified 5-8-membered heterocycle contains 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, such as imidazolyl and the like),

(e) optionally halogenated C1-4alkyloxy,

(f) cyano,

(g) carbamoyl, optionally substituted C1-8the alkyl, and

(h) C1-4alkoxycarbonyl,

(iii) 5-8-membered heterozygosity containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, which is substituted by 1-5 substituents selected from the

(a) halogen,

(b) optionally halogenated C1-4of alkyl,

(c) hydroxy-C1-4of alkyl,

(d) heterocycle-C1-4the alkyl (preferably 5-8-membered heterocycle-C1-4of alkyl, where the decree is hydrated 5-8-membered heterocycle contains 1-3 heteroatoms, selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, such as imidazolyl and the like),

(e) optionally halogenated C1-4alkyloxy,

(f) cyano,

(g) carbamoyl, optionally substituted C1-8the alkyl, and

(h) C1-4alkoxycarbonyl, and

(iv) 5-8-membered heterocycle-C1-3alkyloxy containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, which is substituted by 1-5 substituents selected from the

(a) halogen,

(b) optionally halogenated C1-4of alkyl,

(c) hydroxy-C1-4of alkyl,

(d) heterocycle-C1-4the alkyl (preferably 5-8-membered heterocycle-C1-4of alkyl containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, such as imidazolyl and the like),

(e) optionally halogenated C1-4alkyloxy,

(f) cyano,

(g) carbamoyl, optionally substituted C1-8the alkyl, and

(h) C1-4alkoxycarbonyl;

where C6-18the aryl group optionally substituted by 1-4 substituents selected from halogen and optionally halogenated C1-4of alkyl;

R1represents a hydrogen atom;

R2represents a C1-8alkyl group, a C2-8alkenylphenol group or a C2-8Alki the ilen group, each of which is substituted by substituent(s)selected(s)

(a) hydroxy,

(b) optionally halogenated C1-4alkyloxy,

(c) -O-(CH2)n-OH,

(d) -O-(CH2)n-O-CO-NH2,

(e) -O-(CH2)n-O-C1-4of alkyl,

(f) -O-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(g) -O-(CH2)n-SO2-C6-18aryl,

(h) -O-(CH2)n-SO2-(CH2)n-OH,

(i) -O-(CH2)n-NR8-SO2-(optionally halogenated C1-4the alkyl),

(j) -CO-NR8-(CH2)n-OH,

(k) -CO-NR8-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(l) -NR6R7,

(m) -NR8-(CH2)n-OH,

(n) -NR8-(CH2)n-SO2-C1-4of alkyl,

(o) -NR8-CO-(CH2)n-OH,

(p) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(q) -NR8-CO-(CH2)n-SO-(optionally halogenated C1-4the alkyl),

(r) -NR8-CO-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(s) -NR8-CO-(CH2)n-SO2-C3-8cycloalkyl,

(t) -NR8-CO2-(CH2)n-SO2-C1-4of alkyl,

(u) -NR8-CO-NH-(CH2)n-SO2-C1-4of alkyl,

(v) -NR8-SO2-(CH2/sub> )n-SO2-C1-4of alkyl,

(w) -S-(CH2)n-OH,

(x) -SO-(CH2)n-OH,

(y) -SO2-(CH2)n-OH, and

(z) -NR8-CO-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, which is optionally substituted by substituent(s)selected(s) hydroxy, C1-4the alkyl, optionally oxidized C1-4alkylthio, -CO-C1-4of alkyl, -CO-NH-C1-4of alkyl, -CONH2, -SO2-C1-4of alkyl, -SO2-NH-C1-4of alkyl, -SO2NH2and the like),

where n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, R8represents a hydrogen atom or a C1-4alkyl group and the group (CH2)noptionally substituted C1-4the alkyl or hydroxy;

R3represents a hydrogen atom or a C1-6alkyl group; or

R1and R2not necessarily related to educationor; or

R2and R3not necessarily related to the formation of C2-4alkylene

Particularly preferably, R2represents a C1-8alkyl group, a C2-8alkenylphenol group or a C2-8alkylamino group (in particular, C1-8alkyl group), each of which is substituted by substituent(s)selected(s)

(a) hydroxy,

(b) optionally halogenated C1-4alkyloxy,

(c) -O-(CH2)n-OH (where the group (CH2)noptionally substituted by hydroxy),

(d) -O-(CH2)n-O-CO-NH2,

(e) -O-(CH2)n-O-C1-4of alkyl,

(f) -O-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(g) -O-(CH2)n-SO2-C6-18aryl,

(h) -O-(CH2)n-SO2-(CH2)n-OH,

(i) -O-(CH2)n-NR8-SO2-(optionally halogenated C1-4the alkyl),

(j) -CO-NR8-(CH2)n-OH,

(k) -CO-NR8-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(l) -NR6R7,

(m) -NR8-(CH2)n-OH,

(n) -NR8-(CH2)n-SO2-C1-4of alkyl,

(o) -NR8-CO-(CH2)n-OH (where the group (CH2)noptionally substituted C1-4by alkyl),

(p) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(q) -NR8-CO-(CH2)n-SO-(optionally halogenated C1-4the alkyl),

(r) -N 8-CO-(CH2)n-SO2-(optionally halogenated C1-4the alkyl) (where the group (CH2)noptionally substituted C1-4by alkyl),

(s) -NR8-CO-(CH2)n-SO2-C3-8cycloalkyl,

(t) -NR8-CO2-(CH2)n-SO2-C1-4of alkyl,

(u) -NR8-CO-NH-(CH2)n-SO2-C1-4of alkyl,

(v) -NR8-SO2-(CH2)n-SO2-C1-4of alkyl,

(w) -S-(CH2)n-OH,

(x) -SO-(CH2)n-OH,

(y) -SO2-(CH2)n-OH, and

(z) -NR8-CO-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, which is optionally substituted by substituent(s)selected(s) hydroxy, C1-4the alkyl, optionally oxidized C1-4alkylthio, -CO-C1-4of alkyl, -CO-NH-C1-4of alkyl, -CONH2, -SO2-C1-4of alkyl, -SO2-NH-C1-4of alkyl, -SO2NH2and the like),

where n is an integer from 1 to 4, R6and R7are the same or different and each represents a hydrogen atom or a C1-4alkyl group, and R8represents a hydrogen atom or a 1-4alkyl group and the like.

[Compound (Ik)]

The compound (I), where

R2represents a

(i) C5-8alkyl group, a substituted hydroxy,

(ii) C1-8alkyl group substituted by substituent(s)selected(s)

(a) halogenated C1-4alkyloxy,

(b) -O-(CH2)n-OH,

(c) -O-(CH2)n-O-CO-NH2,

(d) -O-(CH2)n-O-(optionally halogenated C1-4the alkyl),

(e) -O-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(f) -O-(CH2)n-SO2-C6-18aryl,

(g) -O-(CH2)n-NR8-SO2-(optionally halogenated C1-4the alkyl),

(h) -CO-NR8-(CH2)n-OH,

(i) -CO-NR8-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(j) -NR8-(CH2)n-SO2-C1-4of alkyl,

(k) -NR8-CO-(CH2)n-OH,

(l) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(m) -NR8-CO-(CH2)n-SO-(optionally halogenated C1-4the alkyl),

(n) -NR8-CO-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(o) -NR8-CO-(CH2)n-SO2-C3-8cycloalkyl,

(p) -NR8-CO2-(CH2)n-SO2-C1-4of alkyl,

(q) -NR8-CO-NH-(C 2)n-SO2-C1-4of alkyl,

(r) -NR8-SO2-(CH2)n-SO2-C1-4of alkyl,

(s) -S-(CH2)n-OH,

(t) -SO-(CH2)n-OH,

(u) -SO2-(CH2)n-OH, and

(v) -NR8-CO-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, which is optionally substituted by substituent(s)selected(s) hydroxy, C1-4the alkyl, optionally oxidized C1-4alkylthio, -CO-C1-4of alkyl, -CO-NH-C1-4of alkyl, -CONH2, -SO2-C1-4of alkyl, -SO2-NH-C1-4of alkyl, -SO2NH2and the like),

where n is an integer from 1 to 4, R8represents a hydrogen atom or a C1-4alkyl group and the group (CH2)noptionally substituted C1-4the alkyl,

(iii) C2-8alkenylphenol group, optionally substituted hydroxy, or

(iv) C2-8alkylamino group, optionally substituted hydroxy.

Particularly preferably, R2represents a

(i) C5-8alkyl group, a substituted hydroxy,

(ii) C1-8alkyl group substituted by substituent(s)selected(s)

(a) halo is enrevanche C 1-4alkyloxy,

(b) -O-(CH2)n-OH (where the group (CH2)noptionally substituted by hydroxy),

(c) -O-(CH2)n-O-CO-NH2,

(d) -O-(CH2)n-O-(optionally halogenated C1-4the alkyl),

(e) -O-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(f) -O-(CH2)n-SO2-C6-18aryl,

(g) -O-(CH2)n-NR8-SO2-(optionally halogenated C1-4the alkyl),

(h) -CO-NR8-(CH2)n-OH,

(i) -CO-NR8-(CH2)n-SO2-(optionally halogenated C1-4the alkyl),

(j) -NR8-(CH2)n-SO2-C1-4of alkyl,

(k) -NR8-CO-(CH2)n-OH (where (CH2)noptionally substituted C1-4by alkyl),

(l) -NR8-CO-(CH2)n-O-C1-4of alkyl,

(m) -NR8-CO-(CH2)n-SO-(optionally halogenated C1-4the alkyl),

(n) -NR8-CO-(CH2)n-SO2-(optionally halogenated C1-4the alkyl) (where the group (CH2)noptionally substituted C1-4by alkyl),

(o) -NR8-CO-(CH2)n-SO2-C3-8cycloalkyl,

(p) -NR8-CO2-(CH2)n-SO2-C1-4of alkyl,

(q) -NR8-CO-NH-(CH2)n-SO2-C1-4of alkyl,

(r) -NR8-SO2-(CH2) n-SO2-C1-4of alkyl,

(s) -S-(CH2)n-OH,

(t) -SO-(CH2)n-OH,

(u) -SO2-(CH2)n-OH, and

(v) -NR8-CO-(optionally substituted heterocyclic group) (this heterocyclic group preferably is a 5-8-membered heterocyclic group containing 1-3 heteroatoms selected from nitrogen atom, oxygen atom and an optionally oxidized sulfur atom, which is optionally substituted by substituent(s)selected(s) hydroxy, C1-4the alkyl, optionally oxidized C1-4alkylthio, -CO-C1-4of alkyl, -CO-NH-C1-4of alkyl, -CONH2, -SO2-C1-4of alkyl, -SO2-NH-C1-4of alkyl, -SO2NH2and the like),

where n is an integer from 1 to 4 and R8represents a hydrogen atom or a C1-4alkyl group,

(iii) C2-8alkenylphenol group, optionally substituted hydroxy, or

(iv) C2-8alkylamino group, optionally substituted hydroxy.

As salts of the compounds represented by formula (I), you can specify, for example, metal salt, ammonium salt, salt with organic base, salt with inorganic acid, salt with organic acid, salts with basic or acidic amino acid and the like. As preferred examples of the metal salt can be specified, for example, salts of the Christmas metal, such as sodium salt, potassium salt and the like; salts of alkaline earth metals such as calcium salt, magnesium salt, barium salt and the like; aluminum salt and the like. As preferable examples of salts with organic base, you can specify, for example, salts with trimethylamine, triethylamine, pyridine, picoline, 2,6-lutidine, ethanolamine, diethanolamine, triethanolamine, tromethamine [Tris(hydroxymethyl)methylamine], tert-butylamine, cyclohexylamine, dicyclohexylamine, N,N'-dibenziletilendiaminom and the like. As preferable examples of salts with inorganic acid, you can specify, for example, salts with hydrochloric acid, Hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid and the like. As preferable examples of salts with organic acid, you can specify, for example, salts with formic acid, acetic acid, triperoxonane acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, malic acid, methanesulfonic acid, benzosulfimide acid, p-toluensulfonate acid and the like. As preferable examples of salts with basic amino acid, you can specify voltage is emer, salts with arginine, lysine, ornithine and the like, and as preferable examples of salts with acidic amino acid can be specified, for example, salts with aspartic acid, glutamic acid and the like.

Of these salts, preferred are pharmaceutically acceptable salts. For example, when the compound contains an acidic functional group, you can specify inorganic salts such as alkali metal salts (e.g. sodium salt, potassium salt, etc.), salts of alkaline earth metals (e.g. calcium salt, magnesium salt, barium salt etc) and the like, and when the compound contains a basic functional group, there can be mentioned, for example, salts with inorganic acid such as hydrochloric acid, Hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid and the like, or salts with organic acid such as acetic acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, methanesulfonate acid, p-toluensulfonate acid and the like.

As compounds (I), preferred is a compound where a is an aryl group substituted by a group of the formula-Y2-B and optional additional samisen the Yu, where Y2represents a single bond, -O-, -OCH2-, -NH - or-S - and represents an aryl group, a heterocyclic group, a C3-8cycloalkyl group, carbamoyl group, raidgroup, C6-18arylcarbamoyl group or a C6-18aryl-C1-4alkylcarboxylic group, each of which is optionally substituted.

As the preferred option of the compound (I) you can specify the connection, where

W represents C(R1);

But is an aryl group substituted by a group of the formula-Y2-B and optionally additionally substituted, where Y2represents a single bond, -O-, -OCH2-, -NH - or-S - and represents an aryl group, a heterocyclic group, a C3-8cycloalkyl group, carbamoyl group, raidgroup, C6-18arylcarbamoyl group or a C6-18aryl-C1-4alkylcarboxylic group, each of which is optionally substituted;

R1represents a group of formula-X2-R4where X2represents a single bond, -NH - or-O - and R4represents a hydrogen atom or a C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, karbamoilnuyu group, C1-8alkylcarboxylic group, C3-8cycloalkyl group, C6-18aryl group, a C6-18/sub> aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, heterocyclic group, a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted;

R2represents a hydrogen atom or a C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, karbamoilnuyu group, C1-8alkylcarboxylic group, C1-8alkylsulfonyl group, C3-8cycloalkyl group, C6-18aryl group, a C6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, C6-18arylsulfonyl group, heterocyclic group, a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted; and

X1 represents-NR3-where R3represents a hydrogen atom or optionally substituted aliphatic hydrocarbon group.

In another preferred variant of the compound (I) you can specify the connection, where

W represents N;

X1 represents-NR3-where R3is an atom in which Orada or optionally substituted aliphatic hydrocarbon group;

But is an aryl group substituted by a group of the formula-Y2-B and optionally additionally substituted, where Y2represents a single bond, -O-, -OCH2-, -NH - or-S - and represents an aryl group, a heterocyclic group, a C3-8cycloalkyl group, carbamoyl group, raidgroup, C6-18arylcarbamoyl group or a C6-18aryl-C1-4alkylcarboxylic group, each of which is optionally substituted; and

R2represents a hydrogen atom or a C1-8alkyl group, a C2-8alkenylphenol group, C2-8alkylamino group, karbamoilnuyu group, C1-8alkylcarboxylic group, C1-8alkylsulfonyl group, C3-8cycloalkyl group, C6-18aryl group, a C6-18aryl-C1-4alkyl group, a C6-18arylcarbamoyl group, C6-18aryl-C1-4alkylcarboxylic group, C6-18arylsulfonyl group, heterocyclic group, a heterocycle-C1-4alkyl group, getprocessmemoryinfo group or a heterocycle-C1-4alkylcarboxylic group, each of which is optionally substituted.

In another preferred variant of the compound (I) you can specify the connection, where

W represents N;

X1 represents-NR3-;

And represents aryl g is the SCP, substituted group of the formula-Y2-B and optionally additionally substituted, where Y2represents a single bond, -O-, -OCH2-, -NH - or-S - and represents an aryl group, a heterocyclic group, a C3-8cycloalkyl group, carbamoyl group, raidgroup, C6-18arylcarbamoyl group or a C6-18aryl-C1-4alkylcarboxylic group, each of which is optionally substituted; and

R2and R3related to education optionally substituted ring structure.

[Methods of obtaining]

The following steps describe how to obtain the compound (I) of the present invention.

The compound (I) of the present invention can be obtained, for example, by the method shown in subsequent diagrams, or similar method, and the like.

Compounds (II)-(VIII) in the diagrams include the salts and as such can be used, for example, salts, similar to the salts of compound (I), and the like.

Compounds derived at each stage, can be used in the form of a reaction mixture or as a crude product in the next stage. In addition, the connection can be isolated from the reaction mixture using the traditional method and can be easily cleaned partitioning methods, such as recrystallization, distillation, chromatography is like.

Below is shown the scheme of reactions, where each symbol of the compounds is the same as defined above.

The compound (I) of the present invention can be obtained, for example, by the interaction of the compounds represented by the formula:

where L represents a leaving group and other symbols are as defined above, or its salt with a compound represented by the formula:

where G represents a hydrogen atom or a metal atom, and other symbols are as defined above, or its salt.

When X1 represents-NR3-Y1-, -O - or-S-, G is mainly a hydrogen atom, but may be an alkaline metal such as lithium, sodium, potassium, cesium and the like, or an alkaline earth metal such as magnesium, calcium and the like. When X1 represents-CHR3-, G preferably represents a metal, such as lithium, halogenated magnesium, copper, zinc and the like.

The compound (III) or its salt is preferably used in the amount of 1-5 equivalents, preferably 1-2 equivalents, relative to compound (II) and the reaction is preferably carried out in a solvent. In addition, you can use a base or ammonium salt in an amount of about 1-10 equivalents, preferably 1 equivalent.

In the above formula as the leaving group represented by L, it is possible to use a halogen atom such as chlorine, bromine, iodine and the like, a group of the formula: -S(O)kRawhere k is 0, 1 or 2 and Rais a low (C1-4)alkyl group such as methyl, ethyl, propyl and the like, a benzyl group, a C6-10aryl group such as phenyl, tolyl and the like, or a group of the formula: -ORawhere Rais the same as defined above, and the like.

As a solvent in this reaction can be used, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like, aromatic hydrocarbons such as benzene, toluene, xylene and the like, alcohols such as methanol, ethanol, isopropanol, tert-butanol, phenol and the like, ethers such as diethyl ether, tetrahydrofuran, dioxane and the like, acetone, acetonitrile, ethyl acetate, N,N-dimethylformamide, N,N-dimethylacetamide, 1-methyl-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or mixed solvents, and the like.

As the base in this reaction it is possible to use inorganic base, organic base and the like. In particular, it is possible to use, for example, sodium hydroxide, g is droxia potassium, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, triethylamine, N-ethyldiethanolamine, pyridine, N,N-dimethylaminopyridine, sodium methoxide, ethoxide sodium tert-piperonyl potassium, sodium hydride, sodium amide, databaseconnect (DBU) and the like.

As ammonium salts in this reaction can be used pyridine hydrochloride, pyridine hydrobromide, p-toluensulfonate pyridine, quinoline hydrochloride, hydrochloride isoquinoline, pyrimidine hydrochloride, hydrochloride pyrazine, triazine hydrochloride, trimethylamine hydrochloride, triethylamine hydrochloride, the hydrochloride of N-ethyldiethanolamine and the like.

This reaction can be carried out under cooling, at room temperature and when heated (about 40-200°C, preferably about 40-160°C), reaction time is usually about 1-30 hours, preferably about 1 to 20 hours, more preferably about 1-10 hours

The compound (I), where X1 represents-SO - or-SO2-can be obtained by subjecting the compound (I), where X1 represents-S-, reaction of oxidation. As the oxidizing agent can be used, for example, m-chloroperbenzoic acid, hydrogen peroxide, peracetic acid, tert-butylhydroperoxide, peroxosulfates potassium permanganate, perborate sodium, periodate sodium, sodium hypochlorite, halogen and the like. When receiving the soedineniya (I), where X1 represents-SO-, the oxidant is used in an amount of about 1-1 .5 equivalents relative to the starting compound, and when you get the compound (I), where X1 represents-SO2-oxidant is used in an amount of about 2-3 equivalents relative to the starting compound. The solvent for the reaction is not particularly limited, but he would not interacted with the oxidizer, and can be used, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like, aromatic hydrocarbons such as benzene, toluene, xylene and the like, alcohols such as methanol, ethanol, isopropanol, tert-butanol and the like, ethers such as diethyl ether, tetrahydrofuran, dioxane and the like, carboxylic acids such as acetic acid, triperoxonane acid and the like, acetonitrile, ethyl acetate, N,N-dimethylformamide, N,N-dimethylacetamide, 1-methyl-2-pyrrolidone, dimethylsulfoxide, water or mixed solvents, and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time is usually about 1-20 hours, preferably about 1-10 hours

The connection in the scope of the present invention can also be obtained by the application of known methods such as, obtaining the compound (I) is of the present invention for introduction of substituents and conversion of functional groups. For conversion of substituents can be used widely known methods. You can specify, for example, converting to carboxypropyl hydrolysis of ester, conversion to carbamoyl group by amidation of carboxypropyl, conversion to hydroxymethylene group recovery carboxypropyl, conversion to alcohol recovery or alkylation of the carbonyl group, reductive amination of carbonyl group, oxymorphine carbonyl group, the acylation of the amino group, the alkylation of an amino group, substitution and amination of active halogen-amine, alkylation of hydroxy-group, substitution and amination of hydroxy-group, and the like. When the introduction of substituents and conversion of functional groups present reactive Deputy causing adverse reactions, pre reactive Deputy introducing a protective group known in itself by the way, and at the end of the target reaction, the protective group is removed is known in itself by the way, thanks to which it can be obtained the compound of the present invention.

The compound (I), which is the reaction product can be obtained in the form of individual compounds or as a mixture.

The compound (I) of the present invention obtained in the manner described, which may be subjected to known per se influences, such as solvent extraction, concentration, neutralization, filtration, crystallization, recrystallization, column chromatography, high performance liquid chromatography, and the like, resulting target compound can be isolated from the reaction mixture and purified with a high degree of purity.

As the starting compound (III) for this way of getting you can use a commercially available connection or it can be obtained in a known per se method.

The original compound (II) in this way can be obtained, for example, by the method shown in the following diagram. Here the compound (II) comprises the compounds (IIa), (IIb), (IIc), (IId) and (IIe).

where L1and L2represent halogen atoms, Rais the same as defined above, and t is 1 or 2.

In method A, the compound (IIa) can be obtained by interaction of the compound (IV) with a halogenation agent. In method B, the compound (IV) is subjected to interaction with usernames agent to obtain the compound (V), which is then subjected to interaction with the compound represented by the formula, RaL2in the presence of a base to obtain the compound (IIb)which is further subjected to oxidation reaction of obtaining compound (IIc). The method of connection is the group (IIa) is subjected to interaction with the connection, represented by the formula, RaOH, in the presence of a base to obtain compound (IId).

As the halogenation agent in the method And can be used, for example, about 1-100 equivalents of phosphorus oxychloride, pentachloride phosphorus, trichloride phosphorus, thionyl chloride, sulfurylchloride, tribromide phosphorus, and the like. In this case, the reaction can be carried out in the presence of a base, such as diethylaniline, dimethylaniline, pyridine and the like. The reaction can be carried out without solvent, but the solvent for the reaction can be used, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like, aromatic hydrocarbons such as benzene, toluene, xylene and the like, ethers such as diethyl ether, tetrahydrofuran, dioxane and the like, acetonitrile, ethyl acetate, and the like. The reaction is carried out under cooling, at room temperature or when heated, and the reaction time is usually about 1-20 hours, preferably about 1-10 hours

As usernamea agent used at the stage of obtaining the compound (V) from compound (IV) in method B, it is possible to use, for example, about 1-5 equivalents of reagent Lawesson (Lawesson), pentasulfide phosphorus, and the like. As the solvent the reaction can be used, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like, aromatic hydrocarbons such as benzene, toluene, xylene and the like, ethers such as diethyl ether, tetrahydrofuran, dioxane and the like, and the like. The reaction is carried out at room temperature or under heating, and the reaction time is usually about 1-20 hours, preferably about 1-10 hours

As RaL2at the stage of obtaining the compound (IIb) from compound (V) in method B can be used, for example, about 1-5 equivalents under the conditions, benzylchloride, benzylbromide and the like, and as a base can be used, for example, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, triethylamine, N-ethyldiethanolamine, pyridine, N,N-dimethylaminopyridine, sodium methoxide, ethoxide sodium tert-piperonyl potassium, sodium hydride, sodium amide, databaseconnect (DBU) and the like. The solvent can be used, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like, aromatic hydrocarbons such as benzene, toluene, xylene and the like, alcohols such as methanol, ethanol, isopropanol, tert-bout the Nol and the like, ethers, such as diethyl ether, tetrahydrofuran, dioxane and the like, acetone, acetonitrile, ethyl acetate, N,N-dimethylformamide, N,N-dimethylacetamide, 1-methyl-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or mixed solvents, and the like. The reaction is carried out under cooling, at room temperature or when heated, and the reaction time is usually about 1-20 hours, preferably about 1-10 hours

As oxidant on the stage of the compounds (IIb) of the compound (IIc) in method B can be used, for example, m-chloroperbenzoic acid, hydrogen peroxide, peracetic acid, tert-butylhydroperoxide, peroxosulfates potassium permanganate, perborate sodium, periodate sodium, sodium hypochlorite, halogen and the like. When you get a connection (IIc), where t=1, the oxidant is used in an amount of about 1-1 .5 equivalents relative to compound (IIb), and when you get the connection (IIc), where t=2, the oxidant is used in an amount of about 2-3 equivalents relative to compound (IIb). The solvent for the reaction is not particularly limited, but he would not interacted with the oxidizer, and can be used, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like, aromatic hydrocarbons such as benzene, toluene, Xylo and the like, alcohols, such as methanol, ethanol, isopropanol, tert-butanol and the like, ethers such as diethyl ether, tetrahydrofuran, dioxane and the like, carboxylic acids such as acetic acid, triperoxonane acid and the like, acetonitrile, ethyl acetate, N,N-dimethylformamide, N,N-dimethylacetamide, 1-methyl-2-pyrrolidone, dimethylsulfoxide, water or mixed solvents, and the like. The reaction is carried out under cooling, at room temperature or when heated, and the reaction time is usually about 1-20 hours, preferably about 1-10 hours

As RaOH on the stage of the compounds (IIa) of the compound (IId) of the method can be used, for example, about 1-10 equivalents of methanol, ethanol, phenol and the like, and as a base can be used, for example, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, triethylamine, N-ethyldiethanolamine, pyridine, N,N-dimethylaminopyridine, sodium methoxide, ethoxide sodium tert-piperonyl potassium, sodium hydride, sodium amide, databaseconnect (DBU) and the like. The solvent can be used, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like, aromatic hydrocarbons such as be the angry toluene, xylene and the like, ethers such as diethyl ether, tetrahydrofuran, dioxane and the like, acetone, acetonitrile, ethyl acetate, N,N-dimethylformamide, N,N-dimethylacetamide, 1-methyl-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or mixed solvents, and the like. The reaction is carried out under cooling, at room temperature or when heated, and the reaction time is usually about 1-20 hours, preferably about 1-10 hours

In addition, the compound (IV) can be obtained, as shown in the following diagram:

where R10represents a C1-4alkyl group, and other symbols are as defined above.

That is, the compound (VI) is subjected to interaction in the presence of about 1 to 4 equivalents of formamidine or its salt, which may be obtained compound (IV). The solvent can be used, for example, alcohols such as methanol, ethanol, isopropanol, tert-butanol and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like, aromatic hydrocarbons such as benzene, toluene, xylene and the like, ethers such as diethyl ether, tetrahydrofuran, dioxane and the like, acetone, acetonitrile, ethyl acetate, N,N-di is malformed, N,N-dimethylacetamide, 1-methyl-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or mixed solvents, and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time is usually about 1-20 hours, preferably about 1-10 hours

When W represents C(R1), the compound (II) can also be obtained, for example, by the method shown in the following diagram:

where L3represents a halogen atom, and other symbols are as defined above.

In this method, the stage of obtaining the compound (VIII) from compound (VII) can usually be used in the reaction, known as the reaction Sonogashira (Sonogashira), or a similar reaction and usually the compound (VIII) can be obtained by interaction of the compound (VII) from about 1 to 3 equivalents of the compound represented by formulain the presence of a base, about 0.01-1 equivalent of a palladium catalyst and copper iodide. As a basis you can use, for example, triethylamine, N-ethyldiethanolamine, Diisopropylamine, pyridine, N,N-dimethylaminopyridine, databaseconnect (DBU), sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate and the like. As the palladium catalyst, you can use the e l e C for example, dichlorobis(triphenylphosphine)palladium(II), palladium on carbon, palladium diacetate (II), bis(benzonitrile)dichloropalladium(II) and the like. This reaction can be carried out in the joint presence of a tertiary phosphine compounds such as triphenylphosphine, tributylphosphine and the like as a ligand. As solvent for the reaction can be used, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like, aromatic hydrocarbons such as benzene, toluene, xylene and the like, alcohols such as methanol, ethanol, isopropanol, tert-butanol and the like, ethers such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane and the like, acetone, acetonitrile, ethyl acetate, N,N-dimethylformamide, N,N-dimethylacetamide, 1-methyl-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or mixed solvents, and the like. This reaction is carried out at room temperature or under heating, and the reaction time is generally about 1-50 hours, preferably about 1-20 hours

In this method, the stage of obtaining the compound (IIe) from compound (VIII) is usually carried out the reaction of cyclization in the presence of about 1-3 equivalents of base or about 0.01-1 equivalent of copper iodide to obtain compounds the Oia (IIe). As a basis you can use, for example, tert-piperonyl potassium tert-piperonyl sodium tert-piperonyl cesium, ethoxide sodium, potassium hydride, sodium hydride, cesium hydroxide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, triethylamine, N-ethyldiethanolamine, Diisopropylamine, pyridine, N,N-dimethylaminopyridine, databaseconnect (DBU) and the like. As solvent for the reaction can be used, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like, aromatic hydrocarbons such as benzene, toluene, xylene and the like, alcohols such as methanol, ethanol, isopropanol, tert-butanol and the like, ethers such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane and the like, acetone, acetonitrile, ethyl acetate, N,N-dimethylformamide, N,N-dimethylacetamide, 1-methyl-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or mixed solvents, and the like. The reaction is carried out at a low temperature, at room temperature or under heating, and the reaction time is generally about 1-50 hours, preferably about 1-20 hours

Depending on the type of substituent of starting compound (II) starting compound (II)with a different cover up the fir-tree, can be obtained by converting the substituent used as a starting compound, obtained above method of obtaining. To convert Deputy possible to use the well-known General method. You can specify, for example, converting to carbamoyl group by hydrolysis and amidation of ester, conversion to hydroxymethylene group recovery carboxypropyl, conversion to alcohol recovery or alkylation of the carbonyl group, reductive amination of carbonyl group, oxymorphine carbonyl group, the acylation of the amino group, the alkylation of an amino group, substitution and amination of active halogen-amine, alkylation of hydroxy-group, substitution and amination of hydroxy-group, and the like. When the introduction of substituents and conversion of functional groups present reactive Deputy causing adverse reactions in reactive Deputy pre-enter if necessary, the protective group known in itself by the way, and at the end of the target reaction, the protective group is removed is known in itself by the way in which results can also be obtained from the original compound (II).

Obtained in the manner described above, the compound (I) can be isolated and purified known is diversified in itself a method, such as concentration, concentration under reduced pressure, solvent extraction, crystallization, recrystallization, phase transfer, chromatography and the like.

If the compound (I) obtained as a free form, it can be converted into the desired salt, using the known method itself or its modification, and Vice versa, if the compound (I) are obtained in the form of a salt, it can be converted into a free form or another desired salt using known by itself, the method or its modification.

When the compound (I) has isomers such as optical isomer, stereoisomer, isomer position, the rotary isomer and the like, compound (I) includes any isomers and mixtures thereof. For example, when compound (I) has an optical isomer, an optical isomer separated from the racemate, is also included in the scope of compound (I). These isomers can be obtained as independent products are known in itself a method of synthesis or separation method (concentration, solvent extraction, column chromatography, recrystallization and the like).

The compound (I) can be crystalline, and the compound (I) includes both single crystal and a mixture of crystals. Crystals can be obtained by crystallization in accordance with the methods of crystallization, the world is different as such.

The compound (I) can be a MES (e.g., hydrate etc) or desolat, and both are included in the scope of compound (I).

A compound labeled with an isotope (for example,3H,14C,35S125I and the like), is also included in the scope of compound (I).

The prodrug of compound (I) or its salt (hereinafter referred to as compound (I)) means a compound which is converted into compound (I) in the reaction due to an enzyme, gastric acid, etc. under physiological conditions in the living body, that is, a compound which is converted into compound (I) as a result of oxidation, recovery, hydrolysis, etc. according to an enzyme; a compound which is converted into compound (I) by hydrolysis etc. due to gastric acid, etc. the Prodrug of compound (I) may be a compound obtained the exposure of the amino group in compound (I) to acylation, alkylation or phosphorylation (e.g., a compound obtained by exposure of the amino group in compound (I) alzarouni, elavilelavil, intramyocardially, (5-methyl-2-oxo-1,3-dioxolan-4-yl)methoxycarbonylamino, tetrahydrofurfurylamine, pyrrolidinylcarbonyl, pivaloyloxymethyl and tert-bottling plant etc); a compound obtained by the exposure guide is actigraphy in the compound (I) to acylation, alkylation, phosphorylation or boronovanii (e.g., a compound obtained by exposure of the hydroxy-group in the compound (I) acetylation, palmitoylation, propanolamine, pihlajasaari, succinylamino, funeralreview, elavilelavil, dimethylaminocarbonylmethyl etc); a compound obtained by exposure of the carboxyl group in compound (I) esterification or amidation (e.g., a compound obtained by exposure of the carboxyl group in compound (I) utilaterial, phenylacetate, karboksimetilcellyulozih, dimethylaminoethylacrylate, pivaloyloxymethyl, ethoxycarbonylmethylene, feliciaeriksen, (5-methyl-2-oxo-1,3-dioxolan-4-yl)metaliterature, and cyclohexanecarbonitrile metallizirovanaya etc) and the like. Any of these compounds can be obtained from compound (I) in a manner known in itself.

A prodrug for compound (I) may also be a prodrug, which is converted into compound (I) under physiological conditions, such as described in IYAKUHIN no KAIHATSU (Development of Pharmaceuticals), Vol. 7, Design of Molecules, p.163-198, Published by HIROKAWA SHOTEN (1990).

The compound (I) of the present invention or its salt, or prodrug (hereinafter referred to as the compound of the present invention) has inhibi is relevant to tyrosinekinase activity and can be used for prevention or treatment-dependent tyrosine kinase diseases in mammals. Dependent tyrosine kinase diseases include diseases characterized by increased cell proliferation due to the abnormal tyrosine kinase enzyme activity. In addition, the compound of the present invention specifically inhibits HER2 kinase and/or EGER kinase and, therefore, it is also useful as a therapeutic agent to inhibit the growth of malignant tumors expressing HER2 and/or EGER kinase, or a preventive measure to prevent turning gormonzawisimogo cancer in gormononezawisimy cancer. In addition, the compound is useful as pharmaceutical agents because it shows low toxicity (e.g., acute toxicity, chronic toxicity, genetic toxicity, reproductive toxicity, cardiotoxicity, the interaction of pharmaceutical substances, Carcinogenicity and the like), high solubility in water and has excellent displays of resistance, pharmacokinetics (absorption, distribution, metabolism, excretion and the like) and efficiency.

Thus, the connection of the present invention can be used as a safe means for the prevention or treatment of diseases caused by abnormal cell proliferation, such as various types of cancer (particularly breast cancer is elezi, prostate cancer, pancreatic cancer, stomach cancer, lung cancer, cancer of the colon, colorectal cancer, cancer of the esophagus cancer, duodenal cancer, tongue cancer, pharynx cancer, brain tumor, acoustic, non-small cell lung cancer, small cell lung cancer, liver cancer, kidney cancer, bile duct cancer, cancer of the uterus, cervical cancer, ovarian cancer, bladder cancer, skin cancer, hemangioma, malignant lymphoma, malignant melanoma, thyroid cancer, bone tumor, vascular fibroma, retinoblastoma, cancer of the penis, solid cancer in childhood, Kaposi's sarcoma, Kaposi's sarcoma AIDS, maxillary sinuses tumor, fibrous histiocytoma, leiomyosarcoma, rhabdomyosarcoma, leukemia and so on), atherosclerosis, angiogenesis (e.g., angiogenesis associated with growth of solid cancer and sarcoma, angiogenesis associated with tumor metastasis, and angiogenesis associated with diabetic retinopathy, etc) and viral diseases (HIV etc).

Dependent tyrosine kinase diseases include cardiovascular diseases associated with abnormal enzyme activity of tyrosine kinase. The compound of the present invention can therefore be used as a means for prevention or treatment of cardiovascular diseases such as restenosis.

Connected to the e of the present invention is useful as an anticancer tool for the prevention or treatment of cancer, in particular, for example, breast cancer, prostate cancer, pancreatic cancer, stomach cancer, lung cancer, colon cancer, colon cancer, kidney cancer, and the like.

The compound of the present invention shows low toxicity and can be used as a medicine in the form as it is or as a pharmaceutical composition in mixture with well-known pharmaceutically acceptable carrier, etc. in mammals (e.g. humans, horses, cows, dogs, cats, rats, mice, rabbits, pigs, monkeys and the like).

In addition to the compound of the present invention, the specified pharmaceutical composition may contain other active ingredients, such as hormonal therapeutic agents, anticancer agent (e.g., chemotherapeutic drugs, immunotherapy or pharmaceutical agents inhibiting the action of cell growth factors or receptors of growth factors, cells and the like.

As pharmaceutical agents for mammals, such as humans, the compound of the present invention may be administered orally in the form of, for example, tablets, capsules (including soft capsules and microcapsules), powders, granules and the like, or parenterally in the form inye the traditional solutions, suppositories, pills and the like. Examples of parenteral method of administration include intravenous, intramuscular, subcutaneous, intra -, intranasal, intradermal, drip, intracerebrally, intrarectal, intravaginal, intraperitoneally, intratumoral, near tumors and directly in the affected area.

The dose of a compound of the present invention varies depending on the method of administration, symptoms, etc. for Example, when administered orally as anticancer means the patient (body weight 40-80 kg) breast cancer or prostate cancer dose of, for example, 0.5 to 100 mg/kg of body weight per day, preferably 1-50 mg/kg of body weight per day and more preferably 1-25 mg/kg of body weight per day. The specified number may be entered at one time or 2-3 split doses during the day.

The compound of the present invention can be safely administered orally or parenterally (e.g., local, rectal, intravenous administration etc), as individual substances or in the form of a pharmaceutical composition containing a pharmacologically acceptable carrier according to conventional method (for example, by the method described in the Pharmacopoeia of Japan, etc), such as tablet (including tablet with sugar coated tablet film-the opening), powder, granule, capsule, liquid, emulsion, suspension, injection form, suppository, the drug slow-release, patch, and the like.

The combination of (1) introducing an effective amount of the compounds of the present invention and (2) 1-3 action selected from the group consisting of (i) introducing an effective amount of other anti-cancer funds, (ii) introducing an effective amount of hormonal therapeutic agents, and (iii) non-drug therapy can prevent and/or treat cancer more effectively. Examples of non-drug therapies include surgery, radiotherapy, gene therapy, thermotherapy, cryotherapy, laser cauterization, and the like, and can be combined into two or more of these methods.

For example, the compound of the present invention may be introduced to the same subject simultaneously with hormonal therapy, anti-cancer agents (e.g. chemotherapeutics, immunotherapy drugs or pharmaceutical means, any abscopal effect of cell growth factors or receptors of growth factors cells) (hereinafter in this description of these tools is called as concomitant drug).

Although the compound of the present invention exhibits excellent anti-cancer action is satisfied even when used in the form of simple means, its effect may be enhanced when used in combination with one or more of the above concomitant drugs (simultaneous introduction of multiple funds).

As examples of these “hormonal therapeutic agents, you can specify fosfestrol, diethylstilbestrol, hlortrianizen, medroxyprogesterone acetate, acetate megestrol, acetate chlormadinone, acetate ciproteron, danazol, dienoguest, asoprisnil, allylestrenol, gestrinone, nomegestrol, Tadenan, mepartricin, raloxifene, ormeloxifene, levormeloxifene, antiestrogens (for example, tamoxifen citrate, toremifene citrate, and the like), step-down regulator ER (e.g., fulvestrant, and the like), human menopausal gonadotropin, follicle-stimulating hormone preparations in the form of pills, mepitiostane, testolactone, aminoglutethimide, an agonist of LH-RH (for example, goserelin acetate, buserelin, leiprorelina and the like), droloxifene, epitiostanol, ethinylestradiol sulfonate, aromatase inhibitors (for example, patronagebased, anastrozole, letrozol, exemestane, vorozole, formestane, and the like), antiandrogens (for example flutamide, beckertime, nilutamide and the like), inhibitors of 5α-reductase inhibitors (e.g. finasteride, dutasteride, epristeride and the like), adrenocorticotrophin drug with whom estva (for example, dexamethasone, prednisolone, betamethasone, triamcinolone, and the like), inhibitors of the synthesis of androgens (for example, abiraterone and the like), retinoid and drugs that slow retinoid metabolism (e.g., liarozole and the like), etc. and are preferred agonist of LH-RH (e.g., goserelin acetate, buserelin, leiprorelina.

As examples of said “chemotherapeutic agents”, you can specify alkylating tools, antimetabolites, anticancer antibiotics, anticancer agents of vegetable origin, and the like.

As examples of alkylating means” you can specify a nitrogen mustard hydrochloride nitrogen mustard N-oxide, chlorambucil, cyclophosphamide, ifosfamide, thiotepa, carboquone, innoculateit, busulfan, diastereomeric, mitobronitol, melphalan, dacarbazine, ranimustine, estramustine sodium, triethylenemelamine, carmustin, lomustin, streptozocin, pipobroman, etoposide, carboplatin, cisplatin, miraplacid, nedaplatin, oxaliplatin, altretamin, ambamustine, dipropylenetriamine, fotemustine, prednimustine, punitive, ribomustin, temozolomide, treosulfan, trofosfamide, zinostatin stimulater, adozelesin, sistematik, bizelesin and the like.

As examples of antimetabolites, you can specify mercaptopurin is h, 6-mercaptopurine riboside, thioinosine, methotrexate, enocitabine, cytarabine, cytarabine ocfosfate, antituberculotic, 5-FU drugs (e.g., fluorouracil, tegafur, UFT, doxifluridine, carmofur, Gallitzin, Amateur and the like), aminopterin, leucovorin calcium, tabloid, butzin, folinate, calcium, levofolinate-calcium, cladribine, Amateur, fludarabine, gemcitabine, hydroxycarbamide, pentostatin, piritrexim, idoxuridine, mitoguazone, diasorin, ambamustine and the like.

As examples of anti-cancer antibiotics to specify actinomycin D, actinomycin-C, mitomycin-C, chromomycin-A3, bleomycin hydrochloride, bleomycin sulfate, peplomycin sulfate, daunorubicin hydrochloride, doxorubicin hydrochloride, aclarubicin hydrochloride, pirarubicin hydrochloride, epirubicin hydrochloride, neocarzinostatin, mithramycin, carbomycin, calcination, mitotane, zorubicin hydrochloride, mitoxantrone hydrochloride, idarubitsina hydrochloride and the like.

As a “cancer means of plant origin”, you can specify etoposide, etoposide, vinblastine, vincristina, wijesinha, teniposide, paclitaxel, docetaxel, vinorelbine and the like.

As examples of said “immunotherapy (BRM), you can specify picibanil, baptize is, sizofiran, lentinan, ubenimex, interferons, interleukins, microfi-colony stimulating factor, granulocyte-colony stimulating factor, erythropoietin, lymphotoxin, BCG vaccine,Corynebacterium parvum, levamisole, polysaccharide K, procodazole and the like.

“Growth factor” in these “pharmaceuticals, inhibiting the action of cell growth factors or receptors of growth factors cells” can be called any substances that promote cell proliferation, are normally peptides having a molecular weight of not more than 20,000, and able to be active at low concentrations by binding to a receptor, including (1) EGF (epidermal growth factor) or substances possessing substantially similar to him activity [e.g., EGF, heregulin (HER2 ligand), and the like], (2) insulin or substances possessing essentially similar activity [e.g., insulin, IGF (insulin-like growth factor)-1, IGF-2, and the like], (3) FGF (fibroblast growth factor) or substances possessing substantially similar to him activity [e.g., acidic FGF, basic FGF, KGF (keratinocyte growth factor), FGF-10, and the like], (4) other cell growth factors [e.g., CSF (colony stimulating factor), EPO (erythropoietin), IL-2 (interleukin-2), NGF (growth factor nerves), PDGF (growth factor derived from platelets),TGFβ (transforming growth factor β), HGF (a growth factor for hepatocytes), VEGF (vascular endothelial growth factor) and the like] and the like.

As examples of these “receptors of growth factors”, you can specify any receptors capable of contact with the above mentioned growth factors include EGF receptor, heregulin receptor (HER2), insulin receptor, IGF receptor, FGF receptor-1 or FGF receptor-2, and the like.

As examples of said “pharmaceutical agents inhibiting the action of growth factors, cells, you can specify trastuzumab (Herceptin (Herceptin, trademark)): antibody to HER2), imatinib mesilate, ZD1839 or cetuximab, an antibody to VEGF (e.g., bevacizumab), antibody to VEGF receptor, gefitinib, erlotinib and the like.

In addition to the above pharmaceutical drugs, you can use L-asparaginase, Eagleton, procarbazine hydrochloride, protoporphyrin-cobalt complex salt containing divalent mercury hematoporphyrin-sodium, topoisomerase inhibitors I (for example, irinotecan, topotecan, and the like), topoisomerase II inhibitors (e.g., sobuzoxane and the like), inducers of differentiation (e.g., retinoid, vitamin D, and the like), angiogenesis inhibitors (e.g., thalidomide, SU11248, and the like), α-blockers (e.g., tamsulosin hydrochloride, naftopidil, urapidil, alfuzosin, who etretin, prazosin, silodosin and the like), an inhibitor of serine-trionychinae, antagonist endothelioma receptor (e.g., atrasentan and the like), an inhibitor proteasome (e.g., bortezomib, and the like), an inhibitor of Hsp 90 (for example, 17-AAG, and the like), spironolactone, Minoxidil, 11α-hydroxyprogesterone, means inhibiting resorption and the vast bone metastasis (for example, zoledronicaa acid, alendronat acid, pamidronate acid, heteronomy acid, ibandronic acid, chondronova acid) and the like.

Of the above funds preferred as related pharmaceutical drugs are agonist of LH-RH (e.g., gosereline, buserelin, leiprorelina and the like), trastuzumab (antibody to HER2), and the like.

For the combination of the compounds of the present invention and the concomitant drug during the administration of compounds of the present invention and the concomitant drug is not restricted, and the compound of the present invention and a concomitant drug can be administered to the subject simultaneously or at different points in time. The dose of the concomitant drug can be determined in accordance with the clinically used input number or may be suitably selected in dependence the value from the subject, you want to enter the dose, route of administration, disease, combination and the like.

The mode of administration of the compounds of the present invention and the concomitant drug is not particularly limited if only the connection of the present invention and a concomitant drug were with the introduction of the joint. Examples of this mode of administration include the following :

(1) the Compound of the present invention and a concomitant drug are produced at the same time and receive a single drug that is administered. (2) the Compound of the present invention and a concomitant drug are prepared separately and have two kinds of preparations which are administered simultaneously by the same route of administration. (3) the Compound of the present invention and a concomitant drug are prepared separately and have two kinds of drugs that are injected the same way of introduction, but only at different points in time. (4) the Compound of the present invention and a concomitant drug are prepared separately and have two kinds of preparations which are administered simultaneously by different routes of administration. (5) the Compound of the present invention and a concomitant drug are prepared separately and have two kinds of drugs that BB is changed in different ways at different points in time (for example, the compound of the present invention and a concomitant drug is administered in this order or in reverse order).

Examples

The present invention is explained in detail with reference to the following referential examples, examples, examples of compositions and experimental examples, but these examples do not limit the present invention.

Elution in column chromatography in the reference examples and examples, carried out under supervision using TLC (thin layer chromatography). When observed by TLC as plates for TLC used Kieselgel 60F254plate (Merck) or NH plate production F. Fuji Silysia Chemical Ltd., the solvent used as an eluting solvent in column chromatography was used as developing solvent and as a means of detection used a UV detector. As silica gel for the column used Kieselgel 60F254(70-230 mesh) manufactured by F. Merck or Chromatics NH DM1020 (basic silica gel 100-200 mesh) manufactured by F. Fuji Silysia Chemical Ltd.

The NMR spectra shows the proton NMR with tetramethylsilane was as an internal standard when using VARIAN Gemini-200 (200 MHz type spectrometer) or Gemini-300 (300 MHz type spectrometer) or BRUKER AVANCE300 (300 MHz type spectrometer); the values of δ are expressed in ppm

Abbreviations used in the reference examples and examples, are as follows:

s: singlet, Shir.: broad, d: doublet, t: triplet, q: Quartet, DD: double doublet, m: multiplet, J: constant interaction, Hz: Hertz, DMSO: dimethyl sulfoxide.

Methods of genetic manipulation, described in the experimental examples, based on the methods described in Maniatis et al.,Molecular Cloning, Cold Spring Harbor Laboratory, 1989, and in the attached Protocol.

Reference example 1

Getting 2-[(2-chloro-4-nitrophenoxy)methyl]benzonitrile

To a solution of 2-chloro-4-NITROPHENOL (3.5 g) and 2-(methyl bromide)benzonitrile (4.0 g) in N,N-dimethylformamide (50 ml) was added potassium carbonate (3.7 g) and the mixture was stirred at room temperature for 30 minutes after the reaction was added water (50 ml) and the mixture was stirred for 10 min. and the Obtained pale-yellow solid substance was separated by filtration. The residue is washed with diisopropyl ether and dried to obtain specified in the connection header (5,04 g) as pale yellow crystals.

1H-NMR (CDCl3) δ 5,44 (2H, c), 7,13 (1H, d, J=9.0 Hz), 7,51 (1H, dt, J=1,2, 7,2 Hz), 7.68 per-7,80 (3H, m), 8,19 (1H, DD, J=2.7, and 9.0 Hz), 8,35 (1H, d, J=2.7 Hz).

Reference example 2

Getting 2-[(4-amino-2-chlorophenoxy)methyl]benzonitrile

To a solution of 2-[(2-chloro-4-nitrophenoxy)methyl]benzonitrile (2.0 g) in a mixture of ethanol-water (9:1, 40 ml) was added calcium chloride (90% 427 mg) and the mixture was stirred at 100°C for 10 minutes Reduced iron (90%, 2.6 g) was added at room temperature and the mixture was stirred at 100°C for 3 hours after the reaction, the reaction mixture was filtered (celite) and the filtrate was concentrated under reduced pressure. To the residue was added water, the mixture was diluted with ethyl acetate and washed with water and saturated salt solution. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (hexane:ethyl acetate:methylene chloride=2:1:1) to obtain the specified title compound (1.2 g) as a white solid.

1H-NMR (CDCl3) δ of 3.53 (2H, user. c)5,23 (2H, c), is 6.54 (1H, DD, J=2.7, and 8.7 Hz), 6,76 (1H, d, J=2.7 Hz), to 6.88 (1H, d, J=8.7 Hz), 7,42 (1H, dt, J=0,9, and 7.8 Hz), 7,62-of 7.70 (2H, m), 7,81 (1H, d, J=7,8 Hz).

Reference example 3

Getting 2-[(2-methyl-4-nitrophenoxy)methyl]benzonitrile

Specified in the title compound (8.2 g) was obtained as a pale yellow solid interaction on a similar method of reference example 1, using 2-methyl-4-NITROPHENOL (5.0 g) and 2-(methyl bromide)benzonitrile (6.4g).

1H-NMR (CDCl3) δ is 2.37 (3H, c), are 5.36 (2H, c), 6,97 (1H, d, J=8,4 Hz)to 7.50 (1H, m), 7,65-of 7.69 (2H, m), 7,76 (1H, TD, J=0,9, 7.5 Hz), 8,09-to 8.14 (2H, m).

Reference example 4

Getting 2-[(4-amino-2-methylphenoxy)methyl]benzonitrile

Specified in the header of the giving (3.7 g) was obtained as a white solid interaction similar to the method of reference example 2, using 2-[(2-methyl-4-nitrophenoxy)methyl]benzonitrile (6.0 g), calcium chloride (90%, 1.3 g) and recovered iron (90%, 8,3 g).

1H-NMR (CDCl3) δ of 2.24 (3H, c), is 3.41 (2H, user. c)to 5.17 (2H, c), 6,48 (1H, DD, J=3,0, 8,4 Hz), 6,56 (1H, d, J=3.0 Hz), was 6.73 (1H, d, J=8,4 Hz), 7,40 (1H, dt, J=1,2, 7.5 Hz), to 7.59-7,71 (3H, m).

Reference example 5

Obtaining 3-(2-chloro-4-nitrophenoxy)benzonitrile

To a solution of 2-chloro-1-fluoro-4-nitrobenzene (3.7 g) and 3-hydroxybenzonitrile (2.5 g) in N,N-dimethylformamide (50 ml) was added potassium carbonate (4.4 g) and the mixture was stirred at 60°C for 4 hours after the reaction was added water (50 ml) and the mixture was stirred for 10 min. and the Obtained pale-yellow solid substance was separated by filtration, washed with diisopropyl ether and dried to obtain specified in the title compound (5.3 g) as pale yellow crystals.

1H-NMR (CDCl3) δ 7.03 is (1H, d, J=9.0 Hz), 7,27-7,33 (2H, m), 7,55-7,56 (2H, m), 8,15 (1H, DD, J=2.7, and 9.0 Hz), 8,42 (1H, d, J=2.7 Hz).

Reference example 6

Obtaining 3-(4-amino-2-chlorophenoxy)benzonitrile

To a solution of 3-(2-chloro-4-nitrophenoxy)benzonitrile (2.0 g) in a mixture of ethanol-water (9:1, 40 ml) was added calcium chloride (90%, 449 mg) and the mixture was stirred at 100°C for 10 minutes reduced iron (90%, 2.7 g) was added at room temperature and the mixture was stirred at 100°C for 5 hours Upon completion of the reaction, the reaction mixture was filtered (celite) and fil the rat was concentrated under reduced pressure. To the residue was added water, the mixture was diluted with ethyl acetate and washed with water and saturated salt solution. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (hexane:ethyl acetate=3:1) to obtain the specified title compound (1.25 g) as a white solid.

1H-NMR (CDCl3) δ of 3.75 (2H, user. c)6,60 (1H, DD, J=2.7, and an 8.4 Hz), to 6.80 (1H, d, J=2.7 Hz), 6,92 (1H, d, J=8,4 Hz), 7,06 (1H, m), 7,14 (1H, m), 7,30 (1H, TD, J=1,2, 7.5 Hz), 7,37 (1H, d, J=7.5 Hz).

Reference example 7

Getting 2-fluoro-5-nitrotyrosine

Under ice cooling was added dropwise thionyl chloride (8,02 ml) to ethanol (200 ml) and then was added 2-fluoro-5-nitrobenzoic acid (13,81 g). The resulting mixture was stirred at 80°C for 4 h and then concentrated under reduced pressure. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture and the mixture was extracted with ethyl acetate. The extract was washed with saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure to obtain specified in the connection header (15,77 g) as a pale yellow oil.

1H-NMR (CDCl3) δ: USD 1.43 (3H, t, J=7.2 Hz), to 4.46 (2H, q, J=7.2 Hz), 7,32 (1H, t, J=9.1 Hz), to 8.41 (1H, DDD, J=9,1, 4,3, 3.0 Hz), cent to 8.85 (1H, DD, J=6,1, 3,0 Hz).

Reference example 8

A mixture of 2-fluoro-5-nitrotyrosine (1.07 g), phenol (565 mg), potassium carbonate (1,38 g) and N,N-dimethylformamide (20 ml) was stirred at 80°C for 4 h the Reaction mixture was concentrated under reduced pressure. To the residue was added water and the mixture was extracted with ethyl acetate. The extract was washed with saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was purified by chromatography on a column of silica gel (eluent: ethyl acetate:hexane=20:80→30:70). The target fraction was concentrated under reduced pressure and to the residue (1.54 g) was added ethanol (20 ml) and 10% palladium on carbon (1.5 g). The mixture was stirred overnight in a hydrogen flow. The catalyst was filtered and the filtrate was concentrated. The obtained residue was purified by chromatography on a column of silica gel (eluent: ethyl acetate:hexane=20:80→50:50) and recrystallized from a mixture of diisopropyl ether-hexane to obtain specified in the title compound (1.07 g) as pale brown powder.

1H-NMR (CDCl3) δ: of 1.12 (3H, t, J=7.2 Hz), 3,71 (2H, c)to 4.17 (2H, q, J=7.2 Hz), to 6.80-6.87 in (3H, m)6,91 (1H, d, J=8.5 Hz), 6,97 (1H, t, J=7,3 Hz), 7,21-7,30 (3H, m).

Reference example 9

Getting 4-{[7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidine-1-yl]methyl}methylbenzoate and 4-{[7-(methylthio)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]methyl}methylbenzoate

To a solution of 7-(Matilde is)-1H-pyrazolo[4,3-d]pyrimidine (400 mg) in N,N-dimethylformamide (8 ml) was added 60% sodium hydride (98 mg) under ice cooling and the mixture was stirred at room temperature for 10 minutes Then added with ice cooling 4-(methyl bromide)methylbenzoate (606 mg) and the mixture was stirred at room temperature for 30 minutes after the reaction mixture was diluted with ethyl acetate and washed with saturated aqueous sodium hydrogen carbonate solution and saturated salt solution. The organic layer was concentrated under reduced pressure and the residue was subjected to chromatography on a column of silica gel (hexane:ethyl acetate=2:1→1:2) to give 4-{[7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidine-1-yl]methyl}methylbenzoate (251 mg) and 4-{[7-(methylthio)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]methyl}methylbenzoate (450 mg), both in the form of a pale yellow solid substances.

4-{[7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidine-1-yl]methyl}methylbenzoate:1H-NMR (CDCl3) δ a 2.71 (3H, c), with 3.89 (3H, c), to 5.93 (2H, c), 7,22 (2H, d, J=8.1 Hz), 7,98 (2H, d, J=8.1 Hz), 8,23 (1H, c), 8,80 (1H, c).

4-{[7-(methylthio)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]methyl}methylbenzoate:1H-NMR (CDCl3) δ 2,73 (3H, c)to 3.92 (3H, c)5,69 (2H, c), 7,34 (2H, d, J=8,4 Hz), 8,03 (2H, d, J=8,4 Hz), of 8.04 (1H, c), 8,73 (1H, c).

Reference example 10

Getting 2-[7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidine-1-yl]ethylbenzoic and 2-[7-(methylthio)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]ethylbenzoic

To a solution of 7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidine (300 mg) and 2-icatibant (548 mg) in N,N-dimethylformamide (10 ml) was added potassium carbonate (374 mg) and the mixture was stirred at 60°C for 1 h after the reaction to reaction the th mixture was added water. The mixture was diluted with ethyl acetate and washed with water and saturated salt solution. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (hexane:ethyl acetate=3:2) to give 2-[7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidine-1-yl]ethylbenzoic (266 mg) and 2-[7-(methylthio)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]ethylbenzoic (191 mg), both in the form of pale yellow solids:

2-[7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidine-1-yl]ethylbenzoic:1H-NMR (CDCl3) δ of 2.66 (3H, c), 4,78 (2H, t, J=5.4 Hz), is 5.06 (2H, t, J=5.4 Hz), 7,27-7,40 (2H, m), 7,53 (1H, m), a 7.85-7,89 (2H, m), to 8.20 (1H, c), 8,79 (1H, c).

2-[7-(methylthio)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]ethylbenzoic:1H-NMR (CDCl3) δ 2,73 (3H, c), 4.80 to a 4.86 (4H, m), 7,40-7,46 (2H, m), 7,58 (1H, m), 7,94-of 7.97 (2H, m), to 8.20 (1H, c), 8,73 (1H, c).

Reference example 11

Obtain 3-[7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidine-1-yl]propylbenzoate and 3-[7-(methylthio)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]propylbenzoate

3-[7-(Methylthio)-1H-pyrazolo[4,3-d]pyrimidine-1-yl]propylbenzoate (623 mg) and 3-[7-(methylthio)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]propylbenzoate (556 mg), both received in the form of pale yellow solids interaction similar to the method of reference example 10 using 7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidine (600 mg), 3-improvisata (1,15 g) and potassium carbonate (748 mg):

3-[7-(methylthio)-1H-pyrazolo[4,3d]pyrimidine-1-yl]propylbenzoate: 1H-NMR (CDCl3) δ 2.40 a-2,47 (2H, m)to 2.66 (3H, c), 4,42 (2H, t, J=5.7 Hz), 4,88 (2H, t, J=7.2 Hz), 7,42-7,46 (2H, m), EUR 7.57 (1H, m), 7,98-8,02 (2H, m), 8,15 (1H, c), 8,73 (1H, c).

3-[7-(methylthio)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]propylbenzoate:1H-NMR (CDCl3) δ 2,52-of 2.58 (2H, m), of 2.72 (3H, c), 4,39 (2H, t, J=6.0 Hz)and 4.65 (2H, t, J=6.9 Hz), 7,40-7,46 (2H, m), EUR 7.57 (1H, m), of 7.96-8,02 (2H, m), 8,14 (1H, c), 8,71 (1H, c).

Example 1

Obtain hydrochloride of N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

4-Chloro-5H-pyrrolo[3,2-d]pyrimidine (770 mg) and 3-chloro-4-[(3-terbisil)oxy]aniline (2,52 g) was dissolved in 1-methyl-2-pyrrolidone (10 ml) and the mixture was stirred under heating at 140°C for 2.5 hours After cooling to room temperature the mixture was diluted with ethyl acetate (300 ml) and stirred at room temperature for 1 h Precipitated precipitated powder was separated by filtration, washed with ethyl acetate (30 ml) and dried at reduced pressure to obtain specified in the connection header (1,62 g).

1H-NMR (DMSO-d6) δ: 5,27 (2H, c), 6,63 (1H, d, J=3 Hz), 7,0-7,5 (5H, m), 7,78 (1H, DD, J=3 Hz, 9 Hz), 8,00 (1H, m), 8,15 (1H, d, J=3 Hz), 8,79 (1H, c), to 11.79 (1H, user. c).

Example 2

Receive (4-{[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]methyl}phenyl)methanol

(i) Obtain {4-[(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)methyl]phenyl}methanol

4-Chloro-5H-pyrrolo[3,2-d]pyrimidine (07 mg) was dissolved in N,N-dimethylformamide (2 ml), was added potassium carbonate (304 mg) and the mixture was stirred at room temperature for 30 minutes was Added 4-hydroxymethylbenzene (377 mg) and the mixture was stirred at room temperature for 16 hours After dilution with water (30 ml) the mixture was extracted with a mixture of ethyl acetate-tetrahydrofuran (3:1, 80 ml×2). The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by chromatography on a column of silica gel (eluent: hexane:ethyl acetate=80:20→0:100) to obtain the specified title compound (383 mg) in powder form.

1H-NMR(CDCl3) δ: 2,15 (1H, user. c)4,69 (2H, d, J=4 Hz), 5,71 (2H, c), 6,76 (1H, m), 7,06 (2H, d, J=8 Hz), 7,34 (2H, d, J=8 Hz), to 7.50 (1H, d, J=3 Hz), 8,69 (1H, c).

(ii) Receiving (4-{[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]methyl}phenyl)methanol

{4-[(4-Chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)methyl]phenyl}methanol (354 mg) and 3-chloro-4-[(3-terbisil)oxy]aniline (488 mg) was dissolved in 1-methyl-2-pyrrolidone (2,58 ml) and the mixture was stirred under heating at 140°C for 2 hours After cooling to room temperature the reaction mixture was diluted with ethyl acetate (80 ml) and separated with saturated aqueous sodium bicarbonate (30 ml). The organic layer was washed with saturated salt solution (30 ml), dried over magnesium sulfate and concentrated under reduced pressure. The remainder of the division is whether and purified by chromatography on a column of silica gel (eluent: hexane:ethyl acetate=80:20→0:100) to obtain the specified title compound (588 mg) in powder form.

1H-NMR (CDCl3) δ: of 4.77 (2H, c), 5,07 (2H, c), 5,52 (2H, c), of 6.26 (2H, c), only 6.64 (1H, d, J=3 Hz), for 6.81 (1H, d, J=9 Hz)and 6.9 to 7.4 (8H, m), 7,49 (2H, d, J=8 Hz), 8,44 (1H, c).

Example 3

Obtain N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5-(3,4-dimethoxybenzoyl)-5H-pyrrolo[3,2-d]pyrimidine-4-amine

Under ice cooling to a suspension of the hydrochloride of N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine (150 mg) and potassium carbonate (102 mg) in N,N-dimethylformamide (1.5 ml) was added 3,4-dimethoxybenzoate (82 mg) and the mixture was stirred under ice cooling for 1 h, the Mixture was distributed between ethyl acetate (50 ml) and water (30 ml). The organic layer was washed with saturated salt solution (30 ml), dried over magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by chromatography on a column of silica gel (eluent: hexane:ethyl acetate=80:20→ethyl acetate:methanol=80:20) and was led from diisopropyl ether to obtain specified in the title compound (104 mg).

1H-NMR (CDCl3) δ: of 3.97 (3H, c)to 4.01 (3H, c), 5,14 (2H, c), 6,72 (1H, d, J=3 Hz), 6,9-7,6 (10H, m), 7,88 (2H, d, J=3 Hz), 8,63 (1H, c), of 9.75 (1H, user. c).

Example 4

Receive (4-{[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]methyl}phenyl)methanol

Specified in the title compound (242 mg) was obtained as crystals vzaimode esteem similar to the method of example 2 (ii), using {4-[(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)methyl]phenyl}methanol (200 mg), 3-methyl-4-[(6-methylpyridin-3-yl)oxy]aniline (235 mg) and 1-methyl-2-pyrrolidone (1,46 ml).

1H-NMR (CDCl3) δ: 2,14 (3H, c), of 2.50 (3H, c), a 3.01 (1H, user. c), and 4.75 (2H, c), of 5.53 (2H, c), 6,38 (1H, user. c), only 6.64 (1H, d, J=3 Hz), to 6.75 (1H, d, J=9 Hz), 6,8-7,2 (6H, m), 7,34 (2H, d, J=3 Hz), 7,47 (1H, d, J=9 Hz), 8 09 (1H, m), 8,46 (1H, c).

Example 5

Obtain N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

Specified in the title compound (283 mg) was obtained as crystals by the interaction analogous to the methods of example 2 (ii)using 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (200 mg), 3-methyl-4-[(6-methylpyridin-3-yl)oxy]aniline (418 mg) and 1-methyl-2-pyrrolidone (2,6 ml).

1H-NMR (CDCl3) δ: 2,16 (3H, c), of 2.51 (3H, c), 6,56 (1H, d, J=3 Hz), to 6.80 (1H, d, J=9 Hz), 7.0 and about 7.6 (5H, m), 8 17 (1H, m), 8,59 (1H, c), 8,76 (1H, user. c)11,08 (1H, user. c).

Example 6

Getting 4-{[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]methyl}methylbenzoate

(i) Obtaining 4-[(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)methyl]methylbenzoate

Specified in the title compound (1.0 g) was obtained in powder form by interaction, analogous to the methods of example 2 (i)using 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (710 mg), 4-(methyl bromide)methylbenzoate (1.27 g), potassium carbonate (703 mg) and N,N-dime Informatica (9,2 ml).

1H-NMR (CDCl3) δ: 3,90 (3H, c), 5,77 (2H, c), 6,83 (1H, d, J=3 Hz), was 7.08 (2H, d, J=8 Hz), 7,53 (1H, d, J=3 Hz), 8,00 (2H, d, J=8 Hz), 8,73 (1H, c).

(ii) Obtain 4-{[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]methyl}methylbenzoate

Specified in the title compound (1.35 g) was obtained in powder form by interaction, analogous to the methods of example 2 (ii)using 4-[(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)methyl]methylbenzoate (1.0 g), 3-chloro-4-[(3-terbisil)oxy]aniline (1.25 g) and 1-methyl-2-pyrrolidone (6,63 ml).

1H-NMR (CDCl3) δ: 3,93 (3H, c), 5,07 (2H, c), to 5.57 (2H, c), 6,10 (2H, user. c)of 6.68 (1H, d, J=3 Hz), of 6.7 to 7.4 (10H, m), 8,11 (2H, d, J=9 Hz), of 8.47 (1H, c).

Example 7

Getting 4-{[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]methyl}benzoic acid

4-{[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]methyl}methylbenzoate (850 mg) was dissolved in a mixed solvent of ethanol (3,29 ml)-tetrahydrofuran (3,29 ml), was added 1N. an aqueous solution of sodium hydroxide (3,29 ml) and the mixture was stirred at room temperature for 20 hours was Added to the reaction mixture 1H. hydrochloric acid (3,29 ml) and the mixture was diluted with water (20 ml). Precipitated precipitated crystals were separated by filtration, washed with water (10 ml) and dried under reduced pressure to obtain specified in the title compound (738 mg).

1H-NMR (DMSO-d6) δ: to 5.21 (2H, c)5,94 (2H, c), 6,62 (1H, d, J=3 Hz), of 7.0 and 7.6 (9H, m), to 7.84 (2H, d, J=9 Hz), to $ 7.91 (1H, d, J=3 Hz), 8,40 (1H, c), 8,81 (1H, user. c)12,88 (1H, user. c).

Example 8

Obtaining 1-(4-{[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]methyl}benzoyl)piperidine-4-ol

To a mixture of 4-{[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]methyl}benzoic acid (150 mg), 4-hydroxypiperidine (33,2 mg and monohydrate of 1-hydroxybenzotriazole (60 mg) in N,N-dimethylformamide (3 ml) was added the hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (86 mg) and triethylamine (0,208 ml) at room temperature and the mixture was stirred over night at room temperature. The mixture was distributed between ethyl acetate (50 ml) and water (30 ml). The organic layer was washed with saturated salt solution (30 ml), dried over magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by chromatography on a column with a basic silica gel (eluent: ethyl acetate:methanol=100:0→ethyl acetate:methanol=80:20) and was led from diisopropyl ether to obtain specified in the title compound (168 mg).

1H-NMR (CDCl3) δ: 1,4-2,1 (5H, m), of 3.0 to 3.7 (3H, m), of 3.97 (1H, m)to 4.16 (1H, m)5,08 (2H, c), of 5.55 (2H, c), 6,33 (1H, user. c), of 6.66 (1H, d, J=3 Hz), PC 6.82 (1H, d, J=9 Hz), the 6.9 to 7.5 (11H, m), of 8.47 (1H, c).

Example 9

Paul is an increase of 6-(3-AMINOPHENYL)-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

(i) obtaining the hydrochloride of 6-chloro-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-5-nitropyrimidin-4-amine

4,6-Dichloro-5-nitropyrimidine (9.7 g) was dissolved in 1-methyl-2-pyrrolidone (25.7 mm), a solution of 3-methyl-4-[(6-methylpyridin-3-yl)oxy]aniline (5.35 g) in 1-methyl-2-pyrrolidone (10 ml) was added dropwise under cooling at -15°C and the mixture was stirred at a temperature from -10°C to 0°C for 1 h the Mixture was diluted with ethyl acetate (100 ml) and stirred at 0°C within 15 minutes of Precipitated precipitated crystals were separated by filtration, washed with ethyl acetate (30 ml) and dried under reduced pressure to obtain specified in the connection header (7,34 g).

1H-NMR (DMSO-d6) δ: 2,20 (3H, c)to 2.67 (3H, c), 7,0-8,0 (5H, m), 8,44 (1H, m), 8,55 (1H, c), 10,14 (1H, user. c).

(ii) Obtaining 6-chloro-N4-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}pyrimidine-4,5-diamine

The hydrochloride of 6-chloro-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-5-nitropyrimidin-4-amine (2,04 g) suspended in diethyl ether (9,45 ml) and a solution of chloride dihydrate tin(IV) (9,1 g) in concentrated hydrochloric acid (20,17 ml) was added under ice cooling. After stirring at room temperature for 3 h, the reaction mixture was poured into ice water (400 ml). Was added dropwise a 50% aqueous sodium hydroxide solution (18 ml) to bring the pH to 8. Ethyl acetate (300 ml) was added and the mixture was filtered through celite. Organizes the second layer was dried over magnesium sulfate and concentrated under reduced pressure to obtain specified in the title compound (1.30 grams).

1H-NMR (CDCl3) δ: 2,23 (3H, c), 2,52 (3H, c), 6,85 (1H, d, J=9 Hz), 7,0-7,5 (4H, m), 8,16 (1H, c), 8,21 (1H, d, J=3 Hz).

(iii) Obtaining hydroiodide 6-iodine-N4-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}pyrimidine-4,5-diamine

6-Chloro-N4-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}pyrimidine-4,5-diamine (400 mg) suspended in 55% idiscovered acid (6,16 ml), was added sodium iodide (878 mg) and the mixture was stirred under heating at 70°C for 10 min After cooling to room temperature was added a mixture of water (40 ml)-ethyl acetate (30 ml). After adjusting the pH of the mixture to at least 7 aqueous solution of sodium bicarbonate and the mixture was stirred at room temperature for 15 minutes the Organic layer was dried over magnesium sulfate and concentrated under reduced pressure to obtain specified in the header of the compound (626 mg).

1H-NMR (CDCl3) δ: 2,19 (3H, c), 2,52 (3H, c)to 4.23 (2H, user. c), for 6.81 (1H, d, J=9 Hz), 7,0-7,5 (5H, m), of 7.97 (1H, c), 8,18 (1H, d, J=3 Hz).

(iv) Obtain 6-[(3-AMINOPHENYL)ethinyl]-N4-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}pyrimidine-4,5-diamine

Hydroiodide 6-iodine-N4-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}pyrimidine-4,5-diamine (200 mg) was dissolved in a mixed solvent of acetonitrile (7,6 ml)triethylamine (5,72 ml)was sequentially added 3-itinerary (0,0574 ml), TRANS-dichlorobis(triphenylphosphine)palladium(II) (15,4 mg) and copper iodide(I) (5.3 mg) and the mixture was stirred in a stream of nitrogen at room for the Noah temperature for 1,5 hours The reaction mixture was concentrated under reduced pressure, the residue was separated and purified by chromatography on a column of silica gel (eluent: hexane:ethyl acetate=80:20→ethyl acetate:methanol=80:20) to obtain the specified title compound (157 mg).

1H-NMR (CDCl3) δ: 2,19 (3H, c), of 2.51 (3H, c), the 3.65 (2H, user. c)4,37 (2H, user. c)of 6.6 to 7.5 (9H, m)to 7.50 (1H, user. c), 8,19 (1H, d, J=3 Hz), 8,29 (1H, c).

(v) Obtain 6-(3-AMINOPHENYL)-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

6-[(3-AMINOPHENYL)ethinyl]-4-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}pyrimidine-4,5-diamine (140 mg) was dissolved in N,N-dimethylformamide (0,82 ml), was added copper iodide(I) (6.3 mg) and the mixture was stirred in a stream of nitrogen while heating at 110°C for 16 hours After cooling to room temperature the reaction mixture was diluted with dichloromethane (20 ml) and filtered through celite. The filtrate was concentrated under reduced pressure, the residue was separated and purified by chromatography on a column with a basic silica gel (eluent: ethyl acetate:methanol=100:0→85:15) and was led from diisopropyl ether to obtain specified in the title compound (76 mg).

1H-NMR (DMSO-d6) δ: 2,22 (3H, c), is 2.44 (3H, c), 5,32 (2H, user. c)of 6.65 (1H, d, J=7 Hz), 6,76 (1H, d, J=2 Hz), the 6.9 and 7.3 (6H, m), of 7.75 (1H, DD, J=3 Hz, 9 Hz), 7,83 (1H, d, J=2 Hz), 8,18 (1H, d, J=3 Hz), a 8.34 (1H, c), 9,14 (1H, user. c)11,47 (1H, user. c).

Example 10

P is torching 6-(4-AMINOPHENYL)-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

(i) Obtaining 6-[(4-AMINOPHENYL)ethinyl]-N4-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}pyrimidine-4,5-diamine

Hydroiodide 6-Iodine-N4-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}pyrimidine-4,5-diamine (270 mg) was dissolved in a mixed solvent of acetonitrile (10.3 ml)triethylamine (7,72 ml) and the resulting solution was sequentially added 4-itinerary (80,3 mg), TRANS-dichlorobis(triphenylphosphine)palladium(II) (20,8 mg) and copper iodide(I) (7,16 mg). Specified in the title compound (134 mg) was obtained in powder form by interaction, analogous to the methods of example 9 (iv).

1H-NMR (CDCl3) δ: 2,20 (3H, c), of 2.51 (3H, c), of 4.00 (4H, user. c)6,60 (2H, d, J=9 Hz), 6,83 (1H, d, J=9 Hz), 7,0-7,5 (6H, m), 8,21 (1H, m), 8,29 (1H, c).

(ii) Obtaining 6-(4-AMINOPHENYL)-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

Specified in the title compound (68 mg) was obtained in powder form by interaction, analogous to the methods of example 9 (v)using 6-[(4-AMINOPHENYL)ethinyl]-N4-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}pyrimidine-4,5-diamine (160 mg) and copper iodide(I) (7.2 mg).

1H-NMR (DMSO-d6) δ: of 2.21 (3H, c), is 2.44 (3H, c), to 5.58 (2H, user. c)6,70 (2H, d, J=9 Hz), of 6.99 (1H, d, J=2 Hz), 7,20 (2H, m), 7,56 (1H, d, J=9 Hz), of 7.75 (1H, DD, J=2 Hz, 9 Hz), 7,81 (1H, d, J=2 Hz), 8,18 (1H, d, J=2 Hz), 8,32 (1H, c), 9,12 (1H, user. c), 11,38 (1H, user. c).

Example 11

Getting 2-methoxy-N-{4-[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-H-pyrrolo[3,2-d]pyrimidine-6-yl]phenyl}ndimethylacetamide

To a mixture of 6-(4-AMINOPHENYL)-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine (40 mg), methoxybutanol acid (0,0145 ml) and the monohydrate of 1-hydroxybenzotriazole (38 mg) in N,N-dimethylformamide (1.9 ml) was added the hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (54 mg) and triethylamine (0.079 in ml) at room temperature. After stirring overnight at room temperature, the reaction mixture was diluted with dichloromethane (10 ml). The residue was separated and purified by chromatography on a column with a basic silica gel (eluent: ethyl acetate:methanol=100:0→ethyl acetate:methanol=85:15) and was led from diisopropyl ether to obtain specified in the title compound (24 mg).

1H-NMR (DMSO-d6) δ: of 2.21 (3H, c), 2,43 (3H, c), 3,39 (3H, c), Android 4.04 (2H, c)6,91 (1H, d, J=2 Hz), of 6.99 (1H, d, J=9 Hz), 7,20 (2H, m), 7,7-7,9 (6H, m), 8,17 (1H, d, J=3 Hz), with 8.33 (1H, c), 9,07 (1H, user. c), becomes 9.97 (1H, user. c), to 11.52 (1H, user. c).

Example 12

Obtain hydrochloride of 6-(4-methoxyphenyl)-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

(i) Obtaining 6-(4-methoxyphenyl)-5H-pyrrolo[3,2-d]pyrimidine-4-ol

Ethyl 3-amino-5-(4-methoxyphenyl)-1H-pyrrole-2-carboxylate (7.2 g) was dissolved in a mixture of tetrahydrofuran (16 ml)-ethanol (32 ml)was added formamidine (of 3.46 g) and the mixture was stirred at 90°C for 16 hours After cooling to room temperature tetrahed furan evaporated under reduced pressure. The residue was diluted with ethanol (20 ml) and precipitated precipitated powder was separated by filtration, washed with ethanol (15 ml) and dried under reduced pressure to obtain specified in the title compound (769 mg).

1H-NMR (DMSO-d6) δ: of 3.80 (3H, c), 6,76 (1H, c), 6,9-7,1 (3H, m), 7,7-8,0 (2H, m), 11,83 (1H, user. c).

(ii) Obtain 4-chloro-6-(4-methoxyphenyl)-5H-pyrrolo[3,2-d]pyrimidine

6-(4-Methoxyphenyl)-5H-pyrrolo[3,2-d]pyrimidine-4-ol (500 mg) suspended in a mixture of N,N-diethylaniline (1,11 ml)-1,2-dichloroethane (to 3.73 ml)was added phosphorus oxychloride (2,29 ml) and the mixture was stirred under heating at 110°C for 2 hours After cooling to room temperature the reaction mixture was treated with ice water (20 ml) and brought to pH 7 or higher by the addition of aqueous ammonia. After dilution with tetrahydrofuran (500 ml) and the mixture was washed with saturated salt solution (50 ml). The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by chromatography on a column of silica gel (eluent: hexane:ethyl acetate=80:20→20:80) to obtain the specified title compound (25 mg).

1H-NMR (CDCl3) δ: 3,90 (3H, c), 6,92 (1H, c), 7,05 (2H, d, J=9 Hz), 7,71 (2H, d, J=9 Hz), 8,73 (1H, c).

(iii) obtaining the hydrochloride of 6-(4-methoxyphenyl)-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

Specified in the title compound (11 mg) was obtained in the de interaction in crystals similar to the method of example 1, using 4-chloro-6-(4-methoxyphenyl)-5H-pyrrolo[3,2-d]pyrimidine (13 mg), 3-methyl-4-[(6-methylpyridin-3-yl)oxy]aniline (16 mg) and 1-methyl-2-pyrrolidone (0.2 ml).

1H-NMR (DMSO-d6) δ: 2,24 (3H, c), the 2.46 (3H, c), 3,86 (3H, c), 7,02 (1H, c), 7,14 (2H, d, J=9 Hz), 7,26 (2H, m), 7,80 (1H, DD, J=3 Hz, 9 Hz), of 7.90 (1H, d, J=3 Hz), 8,11 (2H, d, J=9 Hz), by 8.22 (1H, d, J=3 Hz), 8,72 (1H, c), 11,54 (1H, user. c).

Example 13

Obtain (2E)-3-[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]-2-propen-1-ol

(i) Obtain (2E)-5-[5-amino-6-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)pyrimidine-4-yl]-2-penten-4-in-1-ol

Hydroiodide 6-iodine-N4-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}pyrimidine-4,5-diamine (507 mg) was dissolved in a mixed solvent of acetonitrile (to 19.4 ml)triethylamine (14,5 ml)was sequentially added 2-penten-4-in-1-ol (106 mg), TRANS-dichlorobis(triphenylphosphine)palladium(II) (38,8 mg) and copper iodide(I) (13,4 mg). Specified in the title compound (373 mg) was obtained in powder form by interaction, analogous to the methods of example 9 (iv).

1H-NMR (DMSO-d6) δ: 2,17 (3H, c), 2,43 (3H, c), of 4.12 (2H, m), 5,52 (2H, user. c)equal to 6.05 (1H, dt, J=2 Hz, 16 Hz), 6,53 (1H, dt, J=5 Hz, 16 Hz), 6,93 (1H, d, J=9 Hz), 7,20 (2H, m), 7,63 (2H, m), of 7.96 (1H, c), of 8.15 (1H, d, J=3 Hz), to 8.57 (1H, user. c).

(ii) Obtain (2E)-3-[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]-2-propen-1-ol

Specified in the title compound (59 mg) who were given the interaction is similar to the method of example 9 (v), using (2E)-5-[5-amino-6-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)pyrimidine-4-yl]-2-penten-4-in-1-ol (200 mg), copper iodide(I) (9.8 mg) and N,N-dimethylformamide (1,29 ml) and crystallization from diisopropyl ether.

1H-NMR (DMSO-d6) δ: 2,20 (3H, c), 2,43 (3H, c), 4,22 (2H, d, J=3 Hz), 6,45 (1H, m), 6,50 (1H, c), to 6.67 (1H, dt, J=16 Hz), 6,98 (1H, d, J=9 Hz), 7,19 (2H, m), 7,72 (1H, DD, J=3 Hz, 9 Hz), 7,80 (1H, d, J=2 Hz), 8,17 (1H, d, J=2 Hz), 8,30 (1H, c), of 9.02 (1H, user. c), 11,30 (1H, user. c).

Example 14

Obtain 6-[3-(aminomethyl)phenyl]-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine(i) to Obtain tert-butyl 3-{[5-amino-6-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)pyrimidine-4-yl]ethinyl}benzylcarbamoyl

Hydroiodide 6-iodine-N4-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}pyrimidine-4,5-diamine (500 mg) was dissolved in a mixed solvent of acetonitrile (14,8 ml)triethylamine (11,0 ml) and successively added tert-butyl 3-ethynylbenzaldehyde (247 mg), TRANS-dichlorobis(triphenylphosphine)palladium(II) (31,3 mg) and copper iodide(I) (10,2 mg Specified in the title compound (376 mg) was obtained in the form powder interaction similar to the method of example 9 (iv).

1H-NMR (CDCl3) δ: of 1.47 (9H, c), 2,24 (3H, c), of 2.53 (3H, c), of 4.00 (2H, user. c), 4,32 (2H, d, J=6 Hz), 5,04 (1H, user. c)6,87 (1H, d, J=9 Hz), 7,01 (1H, user. c)7,09-to 7.5 (9H, m), by 8.22 (1H, d, J=2 Hz), a 8.34 (1H, c).

(ii) Obtain tert-butyl 3-[4-({3-methyl-4-[(6-methylpyridin-3-the l)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]benzylcarbamoyl

Specified in the title compound (287 mg) was obtained in powder form by interaction, analogous to the methods of example 9 (v)using tert-butyl 3-{[5-amino-6-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)pyrimidine-4-yl]ethinyl}benzylcarbamoyl (363 mg) and copper iodide(I) (12.9 mg).

1H-NMR (CDCl3) δ: for 1.49 (9H, c)2,17 (3H, c), of 2.51 (3H, c)to 4.23 (2H, user. c)5,67 (1H, user. c)6,72 (1H, c), PC 6.82 (1H, d, J=8 Hz)and 6.9 to 7.7 (8H, m), 8,16 (1H, user. c)at 8.60 (1H, c), 8,66 (1H, user. c)at 10.64 (1H, user. c).

(iii) Obtaining 6-[3-(aminomethyl)phenyl]-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

tert-Butyl 3-[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]benzylcarbamoyl (230 mg) suspended in tetrahydrofuran (2.3 ml)was added 2n. hydrochloric acid (2.3 ml) and the mixture was stirred under heating at 60°C for 3 hours After cooling to room temperature was added 1N. aqueous sodium hydroxide solution (4.6 ml) and the mixture was stirred at room temperature for 5 minutes the Solvent was removed by decantation and the residue was dissolved in tetrahydrofuran (30 ml), dried over potassium carbonate and concentrated under reduced pressure. The residue is triturated in diisopropyl ether, separated by filtration and dried under reduced pressure to obtain specified in the title compound (164 mg).

1H-NMR (DMSO-d6) δ: 2,18 (3H, c), 41 (3H, c)to 3.92 (2H, user. c)a 4.86 (2H, user. c), 6,9-8,2 (11H, m), with 8.33 (1H, c), 9,62 (1H, user. c), 12,13 (1H, user. c).

Example 15

Getting 2-methoxy-N-{3-[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]benzyl}ndimethylacetamide

Specified in the title compound (56 mg) was obtained by interaction similar to the method of example 11 using 6-[3-(aminomethyl)phenyl]-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine (50 mg), methoxybutanol acid (0,01055 ml), monohydrate of 1-hydroxybenzotriazole (23,2 mg), N,N-dimethylformamide (2.3 ml), hydrochloride 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (32,9 mg) and triethylamine (0,080 ml).

1H-NMR (DMSO-d6) δ: of 2.27 (3H, c), 2,52 (3H, c), 3,44 (3H, c), 3,98 (2H, c), 4,56 (2H, d, J=6 Hz), of 6.65 (1H, c), PC 6.82 (1H, d, J=2 Hz), 6,93 (1H, d, J=8 Hz), 7,11 (2H, m), 7,3-7,9 (6H, m), by 8.22 (1H, m), of 8.47 (1H c), 8,82 (1H, user. c)of 11.26 (1H, user. c).

Example 16

Getting 6-(aminomethyl)-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

(i) Obtaining tert-butyl 3-[5-amino-6-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)pyrimidine-4-yl]-2-propionylcarnitine

Hydroiodide 6-iodine-N4-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}pyrimidine-4,5-diamine (500 mg) was dissolved in a mixed solvent of acetonitrile (14,8 ml)triethylamine (11,0 ml) and successively added tert-butyl 2-PROPYNYL arbamate (166 mg), TRANS-dichlorobis(triphenylphosphine)palladium(II) (31,3 mg) and copper iodide(I) (10,2 mg). Specified in the title compound (303 mg) was obtained in powder form by interaction, analogous to the methods of example 9 (iv).

1H-NMR (CDCl3) δ: of 1.46 (9H, c), 2,22 (3H, c), 2,52 (3H, c)4,06 (2H, user. c)to 4.17 (2H, d, J=6 Hz), 5,09 (1H, user. c)at 6.84 (1H, d, J=9 Hz), 7,0 - 7,5 (4H, m), to 8.20 (1H, d, J=3 Hz), of 8.25 (1H, c).

(ii) Obtain tert-butyl[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]methylcarbamate

Specified in the title compound (212 mg) was obtained in powder form by interaction, analogous to the methods of example 9 (v)using tert-butyl 3-[5-amino-6-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)pyrimidine-4-yl]-2-propionylcarnitine (286 mg) and copper iodide(I) (11.8 mg).

1H-NMR (CDCl3) δ: to 1.38 (9H, c), of 2.20 (3H, c), 2,52 (3H, c), 4,30 (2H, d, J=6 Hz), 5,38 (1H, t, J=6 Hz), 6,32 (1H, user. c)6,83 (1H, d, J=9 Hz), 7,07 (1H, d, J=9 Hz), and 7.1 to 7.4 (4H, m), to 7.84 (1H, user. c)to 8.20 (1H, d, J=2 Hz)and 8.50 (1H, c), for 9.95 (1H, user. c).

(iii) Obtaining 6-(aminomethyl)-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

Specified in the title compound (160 mg) was obtained in powder form by interaction, analogous to the methods of example 14 (iii)using tert-butyl[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]methylcarbamate (165 mg), 2n. hydrochloric acid (1,92 ml) and tetrahydrofuran (1,92 ml.

1H-NMR (DMSO-d6) δ: 2,17 (3H, c), 2,42 (3H, c)and 3.59 (2H, t, J=6 Hz), 3,95 (2H, c), and 6.25 (1H, c)6,86 (1H, c)6,94 (1H, d, J=8 Hz), 7,1-7,3 (2H, m), 7,78 (2H, m)to 8.14 (1H, d, J=3 Hz), compared to 8.26 (1H, c), 9,46 (1H user. c), 11,50 (1H, user. c).

Example 17

Obtain (2E)-4-(dimethylamino)-N-{[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]methyl}-2-butanamide

Specified in the title compound (32 mg) was obtained by interaction similar to the method of example 11 using 6-(aminomethyl)-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine (40 mg), hydrochloride (2E)-4-(dimethylamino)-2-butenova acid (22 mg), monohydrate of 1-hydroxybenzotriazole (22,5 mg), N,N-dimethylformamide (2.2 ml), hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (31.9 per mg) and triethylamine (0,0928 ml).

1H-NMR (DMSO-d6) δ: 2,15 (6H, c), are 2.19 (3H, c), 2,43 (3H, c), a 3.01 (2H, d, J=5 Hz), 4,55 (2H, d, J=5 Hz), 6,12 (1H, d, J=16 Hz), 6,36 (1H, d, J=1 Hz), of 6.68 (1H, m), of 6.96 (1H, d, J=8 Hz), 7,18 (2H, m), 7,74 (2H, m), 8,16 (1H, d, J=3 Hz), 8,30 (1H, c), to 8.70 (1H, t, J=5 Hz), of 9.30 (1H, user. c)11,03 (1H, user. c).

Example 18

Obtain 6-[(1E)-3-amino-1-propen-1-yl]-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

(i) Obtain (2E)-5-[5-amino-6-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)pyrimidine-4-yl]-2-penten-4-in-1-iltram-BUTYLCARBAMATE

Hydroiodide 6-iodine-N4-{3-methyl-4-[(6-methylp ridin-3-yl)oxy]phenyl}pyrimidine-4,5-diamine (500 mg) was dissolved in a mixed solvent of acetonitrile (14,8 ml)triethylamine (11,0 ml) and sequentially added (2E)-2-penten-4-in-1-iltram-BUTYLCARBAMATE (194 mg), TRANS-dichlorobis(triphenylphosphine)palladium(II) (31,3 mg) and copper iodide(I) (10,2 mg). Specified in the title compound (199 mg) was obtained in powder form by interaction, analogous to the methods of example 9 (iv).

1H-NMR (CDCl3) δ: of 1.46 (9H, c), of 2.20 (3H, c), 2,52 (3H, c), 3,85 (2H, m), 4,22 (2H, user. c)5,02 (1H, user. c)of 5.84 (1H, d, J=16 Hz), of 6.29 (1H, m), at 6.84 (1H, d, J=9 Hz), 7,0-7,5 (5H, m), 8,19 (1H, d, J=2 Hz), compared to 8.26 (1H, c).

(ii) Obtain (2E)-3-[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]-2-proprietry-BUTYLCARBAMATE

Specified in the title compound (66 mg) was obtained in powder form by interaction, analogous to the methods of example 9 (v)using (2E)-5-[5-amino-6-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)pyrimidine-4-yl]-2-penten-4-in-1-iltram-BUTYLCARBAMATE (195 mg) and copper iodide(I) (7,63 mg).

1H-NMR (CDCl3) δ: the 1.44 (9H, c)a 2.12 (3H, c), 2,49 (3H, c), 3,82 (2H, user. c)of 5.53 (1H, user. c)to 6.00 (1H, d, J=16 Hz), 6,36 (1H, m), 6,77 (1H, d, J=9 Hz), 7,0-7,5 (4H, m), of 8.09 (1H, c), 8,43 (1H, user. c)8,51 (1H, user. c)11,00 (1H, user. c).

(iii) Obtaining 6-[(1E)-3-amino-1-propen-1-yl]-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

Specified in the title compound (41 mg) was obtained in powder form by interaction, analogous to the methods of example 14 (iii), using (2E)-3-[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]-2-proprietry-BUTYLCARBAMATE (65 mg), 2n. floristware the Noah acid (0,755 ml) and tetrahydrofuran (0,755 ml).

1H-NMR (DMSO-d6) δ: 2,17 (3H, c), 2,42 (3H, c), is 3.41 (2H, m), 6,40 (1H, c), 6,62 (2H, m), of 6.96 (1H, d, J=8 Hz), 7,17 (2H, m), 7,95 (2H, m), 8,16 (1H, d, J=3 Hz), of 8.28 (1H, c), of 10.09 (1H, user. c), 12,43 (1H, user. c).

Example 19

Getting 2-methoxy-N-{(2E)-3-[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]-2-propenyl}ndimethylacetamide

Specified in the title compound (15 mg) was obtained by interaction similar to the method of example 11 using 6-[(1E)-3-aminopropan-1-yl]-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine (50 mg), methoxybutanol acid (0,0119 ml), monohydrate of 1-hydroxybenzotriazole (26,2 mg), N,N-dimethylformamide (2,56 ml), the hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (37,2 mg) and triethylamine (0,090 ml).

1H-NMR (DMSO-d6) δ: 2,20 (3H, c), 2,43 (3H, c)to 3.36 (3H, c), 3,88 (2H, c), of 3.97 (2H, t, J=5 Hz), 6,32 (1H, m), of 6.49 (1H, d, J=1 Hz), 6,56 (1H, d, J=17 Hz), 6,97 (1H, d, J=9 Hz), 7,19 (2H, m), of 7.75 (2H, m), of 8.15 (1H, d, J=2 Hz), 8,24 (1H, t, J=5 Hz), 8,29 (1H, c), 9,04 (1H, user. c), 11,33 (1H, user. c).

Example 20

Obtain (2E)-3-[5-ethyl-4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]-2-propen-1-ol

(i) Obtaining 4-iodine-6-phenoxypyridine-5-amine

4,6-Diatpillen-5-amine (2.2 g) was dissolved in 1-methyl-2-pyrrolidone (11.5 ml)was added phenol (656 mg) and potassium carbonate (964 mg) and the mixture was stirred at 100°C for the tion 16 PM After cooling to room temperature the mixture was diluted with ethyl acetate (200 ml) and washed successively with water (100 ml) and saturated salt solution (100 ml). The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by chromatography on a column of silica gel (eluent: hexane:ethyl acetate=80:20→20:80) to obtain the specified title compound (2.0 g) as oil.

1H-NMR (CDCl3) δ: 4,34 (2H, user. c)and 7.1 and 7.5 (5H, m), 7,87 (1H, c).

(ii) Obtaining 4-((3E)-5-{[tert-butyl(dimethyl)silyl]oxy}-3-penten-1-inyl)-6-phenoxypyridine-5-amine

4-Iodine-6-phenoxypyridine-5-amine (1.0 g) was dissolved in a mixed solvent of acetonitrile (53 ml)triethylamine (39 ml) and successively added tert-butyl(dimethyl)[(2E)-2-penten-4-ynyloxy]silane (753 mg), TRANS-dichlorobis(triphenylphosphine)palladium(II) (112 mg) and copper iodide(I) (36,5 mg). Specified in the title compound (1.07 g) was obtained as crystals by the interaction analogous to the methods of example 9 (iv).

1H-NMR (CDCl3) δ: 0,09 (6H, c)of 0.93 (9H, c), 4,32 (2H, m), 4,42 (2H, user. c)between 6.08 (1H, dt, J=16 Hz, 3 Hz), 6.48 in (1H, dt, J=16 Hz, 4 Hz), 7,1-7,5 (5H, m), 8,11 (1H, c).

(iii) Obtaining 6-((1E)-3-{[tert-butyl(dimethyl)silyl]oxy}-1-propenyl)-4-phenoxy-5H-pyrrolo[3,2-d]pyrimidine

Specified in the title compound (409 mg) was obtained in powder form by interaction, analogous to the methods of example 9 (v)using EQ is whether the 4-((3E)-5-{[tert-butyl(dimethyl)silyl]oxy}-3-penten-1-inyl)-6-phenoxypyridine-5-amine (950 mg) and copper iodide(I) (47,4 mg).

1H-NMR (CDCl3) δ: 0,12 (6H, c)of 0.95 (9H, c), 4,39 (2H, m), 6,44 (1H, dt, J=16 Hz, 4 Hz), to 6.67 (2H, m)and 7.1 and 7.5 (5H, m), 8,48 (1H, c), 9,07 (1H, user. c).

(iv) Obtaining 6-((1E)-3-{[tert-butyl(dimethyl)silyl]oxy}-1-propenyl)-5-ethyl-4-phenoxy-5H-pyrrolo[3,2-d]pyrimidine

6-((1E)-3-{[tert-Butyl(dimethyl)silyl]oxy}-1-propenyl)-4-phenoxy-5H-pyrrolo[3,2-d]pyrimidine (100 mg) was dissolved in N,N-dimethylformamide (of 0.786 ml), was added cesium carbonate (102,6 mg) and the mixture was stirred at room temperature for 20 min Iodate (0,0231 ml) was added and the mixture was stirred at room temperature for 2 h and at 40°C for 4 h, After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (50 ml) and washed successively with water (30 ml) and saturated salt solution (30 ml). The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by chromatography on a column of silica gel (eluent: hexane:ethyl acetate=80:20→50:50) to obtain the specified title compound (79 mg) as oil.

1H-NMR (CDCl3) δ: 0,14 (6H, c)to 0.97 (9H, c)of 1.44 (3H, t, J=7 Hz), of 4.44 (2H, m)to 4.52 (2H, q, J=7 Hz), to 6.58 (1H, dt, J=15 Hz, 4 Hz), 6,74 (1H, c), is 6.78 (1H, m), 7,2-7,5 (5H, m), to 8.41 (1H, c).

(v) Obtain (2E)-3-[5-ethyl-4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]-2-propen-1-ol

A mixture of 6-((1E)-3-{[tert-butyl(dimethyl)silyl]oxy}-1-propenyl)-5-ethyl-4-phenoxy-5H-PI is Rolo[3,2-d]pyrimidine (78 mg), 3-methyl-4-[(6-methylpyridin-3-yl)oxy]aniline (61,2 mg), pyridine hydrochloride (26 mg) and phenol (122 mg) was stirred under heating at 120°C for 16 hours After cooling to room temperature the mixture was diluted with dichloromethane (30 ml) and washed with saturated aqueous sodium hydrogen carbonate (20 ml). The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by chromatography on a column with a basic silica gel (eluent: ethyl acetate:methanol=100:0 → 80:20) to obtain the specified title compound (32 mg) in powder form.

1H-NMR (CDCl3) δ: of 1.46 (3H, t, J=7 Hz), 2,24 (3H, c), of 2.53 (3H, c), or 4.31 (2H, q, J=7 Hz), 4,42 (1H, DD, J=5 Hz, 2 Hz), is 6.54 (1H, dt, J=15 Hz, 5 Hz), 6,66 (1H, c), 6,70 (1H, d, J=15 Hz), to 6.88 (1H, d, J=8 Hz,), 7,0-7,4 (4H, m), to 8.20 (1H, d, J=2 Hz), 8,46 (1H, c).

Example 21

Getting hydrochloride [4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]methanol

(i) Obtaining 3-(5-amino-6-phenoxypyridine-4-yl)-2-propyne-1-ol

4-Iodine-6-phenoxypyridine-5-amine (3.0 g) was dissolved in a mixed solvent of acetonitrile (159 ml)triethylamine (117 ml) and sequentially added 2-propyne-1-ol (0,669 ml), TRANS-dichlorobis(triphenylphosphine)palladium(II) (336 mg) and copper iodide(I) (109,5 mg). Specified in the header connection (2,02 g) was obtained as crystals by the interaction on the same methodology note the RA 9 (iv).

1H-NMR (CDCl3) δ: of 3.53 (1H, user. c)to 4.52 (2H, user. c)4,63 (2H, user. c)and 7.1 and 7.5 (5H, m), of 8.09 (1H, c).

(ii) Receiving (4 phenoxy-5H-pyrrolo[3,2-d]pyrimidine-6-yl)methanol

Specified in the title compound (1.31 g) was obtained as crystals by the interaction analogous to the methods of example 9 (v), using 3-(5-amino-6-phenoxypyridine-4-yl)-2-propyne-1-ol (1.98 g) and copper iodide(I) (156 mg).

1H-NMR (DMSO-d6) δ: 4,67 (2H, d, J=5 Hz), the 5.45 (1H, t, J=5 Hz), 6,50 (1H, c), a 7.2 to 7.5 (5H, m), compared to 8.26 (1H, c), 12,15 (1H, user. c).

(iii) Obtaining hydrochloride [4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]methanol

Specified in the title compound (142 mg) was obtained as crystals by the interaction analogous to the methods of example 1 using (4-phenoxy-5H-pyrrolo[3,2-d]pyrimidine-6-yl)methanol (100 mg), 3-chloro-4-[(3-terbisil)oxy]aniline (156 mg), pyridine hydrochloride (56,7 mg) and 1-methyl-2-pyrrolidone (0,828 ml).

1H-NMR (DMSO-d6) δ: was 4.76 (2H, c), 5,27 (2H, c), of 6.50 (1H, d, J=2 Hz), and 7.1 and 7.6 (5H, m), 7,73 (1H, DD, J=3 Hz, 9 Hz), to 8.12 (1H, d, J=3 Hz), 8,77 (1H, c), 11,50 (1H, user. c).

Example 22

Obtain (2E)-3-[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5-methyl-5H-pyrrolo[3,2-d]pyrimidine-6-yl]-2-propen-1-ol

(i) Obtain (2E)-5-(5-amino-6-phenoxypyridine-4-yl)-2-penten-4-in-1-ol

4-Iodine-6-phenoxypyridine-5-amine (3.5 g) was dissolved in a mixed solvent of acetonitrile (18 ml)triethylamine (136 ml) and sequentially added 2-penten-4-in-1-ol (1.1 g), TRANS-dichlorobis(triphenylphosphine)palladium(II) (392 mg) and copper iodide(I) (127 mg). Specified in the header connection (1,79 g) was obtained in powder form by interaction, analogous to the methods of example 9 (iv).

1H-NMR (CDCl3) δ: 2,48 (1H, user. c)to 4.33 (2H, DD, J=5 Hz, 2 Hz), of 4.45 (2H, user. c), 6,12 (1H, dt, J=2 Hz, 16 Hz), is 6.54 (1H, dt, J=16 Hz, 5 Hz), 7,1-7,5 (5H, m), 8,11 (1H, c).

(ii) Obtain (2E)-3-(4-phenoxy-5H-pyrrolo[3,2-d]pyrimidine-6-yl)-2-propen-1-ol

Specified in the title compound (1.25 g) was obtained as crystals by the interaction analogous to the methods of example 9 (v)using (2E)-5-(5-amino-6-phenoxypyridine-4-yl)-2-penten-4-in-1-ol (1.7 g) and copper iodide(I) (268 mg).

1H-NMR (CDCl3) δ: of 2.38 (1H, user. c)to 4.41 (2H, d, J=4 Hz), to 6.58 (1H, dt, J=3 Hz, 16 Hz), 6,66 (1H, c), of 6.75 (1H, d, J=16 Hz), 7,2-7,5 (5H, m), 8,48 (1H, c), 9,73 (1H, user. c).

(iii) Obtain (2E)-3-(4-phenoxy-5H-pyrrolo[3,2-d]pyrimidine-6-yl)-2-propylbenzoate

(2E)-3-(4-Phenoxy-5H-pyrrolo[3,2-d]pyrimidine-6-yl)-2-propen-1-ol (1.0 g) is suspended in tetrahydrofuran (20 ml) and sequentially added triethylamine (0,651 ml) and benzoyl chloride (0,86 ml) under cooling with ice. The mixture was stirred under ice cooling for 2 h, diluted with ethyl acetate (200 ml) and washed with water (50 ml). The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by chromatography on a column with a basic silica gel (eluent: hexanitrate=80:20→0:100) to obtain the specified title compound (1.08 g) as crystals.

1H-NMR (CDCl3) δ: 5,03 (2H, d, J=6 Hz), of 6.52 (1H, m), 6,72 (1H, dt, J=16 Hz, 2 Hz), to 6.80 (1H, d, J=16 Hz), and 7.1 to 7.7 (8H, m), 8,08 (2H, m), and 8.50 (1H, c), 9,27 (1H, user. c).

(iv) Obtain (2E)-3-(5-methyl-4-phenoxy-5H-pyrrolo[3,2-d]pyrimidine-6-yl)-2-propylbenzoate

(2E)-3-(4-Phenoxy-5H-pyrrolo[3,2-d]pyrimidine-6-yl)-2-propylbenzoate (500 mg) was dissolved in N,N-dimethylformamide (4 ml) and sequentially added potassium carbonate (279 mg) and itmean (0.1 ml). After stirring at room temperature for 4 h, water (30 ml) was added to the reaction mixture and the mixture was extracted with ethyl acetate (100 ml), dried over magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by chromatography on a column with a basic silica gel (eluent: hexane:ethyl acetate=80:20→50:50) to obtain the specified title compound (301 mg) in the form of crystals.

1H-NMR (CDCl3) δ: 4,14 (3H, c), to 5.08 (2H, DD, J=6 Hz, 1 Hz), 6,66 (1H, m), at 6.84 (1H, c), 6,85 (1H, d, J=16 Hz), of 7.2 to 7.7 (8H, m), 8,10 (2H, d, J=9 Hz), 8,42 (1H, c).

(v) Obtain (2E)-3-[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5-methyl-5H-pyrrolo[3,2-d]pyrimidine-6-yl]-2-propen-1-ol

A mixture of (2E)-3-(5-methyl-4-phenoxy-5H-pyrrolo[3,2-d]pyrimidine-6-yl)-2-propylbenzoate (100 mg), 3-chloro-4-[(3-terbisil)oxy]aniline (130 mg), pyridine hydrochloride (36 mg) and 1-methyl-2-pyrrolidone (0,518 ml) was stirred under heating at 140°C for 4 h After cooling to room temperature, to the reaction Speedball aqueous solution of sodium bicarbonate (20 ml) and the mixture was extracted with ethyl acetate (100 ml). The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in a mixture of tetrahydrofuran (0,518 ml)-ethanol (0,518 ml), was added 1N. an aqueous solution of sodium hydroxide (0,518 ml) and the mixture was stirred at room temperature for 2 hours was Added to a mixture of tetrahydrofuran-ethyl acetate (1:1, 50 ml) and saturated salt solution (30 ml) and the mixture was extracted. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by chromatography on a column with a basic silica gel (eluent: ethyl acetate:methanol=100:0 → 85:15) to obtain the specified title compound (45 mg) as crystals.

1H-NMR (DMSO-d6) δ: 4,00 (3H, c), is 4.21 (2H, t, J=4 Hz), 5,07 (1H, t, J=5 Hz), 5,23 (2H, c), to 6.58 (1H, m), of 6.68 (1H, c), to 6.80 (1H, d, J=16 Hz), a 7.1 to 7.8 (7H, m), 8,21 (1H, c), 8,49 (1H, user. c).

Example 23

Obtain (2E)-3-[5-methyl-4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]-2-propen-1-ol

Specified in the title compound (60 mg) was obtained as crystals by the interaction is similar to the method of example 22 (v), using (2E)-3-(5-methyl-4-phenoxy-5H-pyrrolo[3,2-d]pyrimidine-6-yl)-2-propylbenzoate (100 mg), 3-methyl-4-[(6-methylpyridin-3-yl)oxy]aniline (111 mg), pyridine hydrochloride (36 mg) and 1-methyl-2-pyrrolidone (0,518 ml).

1H-NMR (DMSO-d6 ) δ: 2,16 (3H, c), 2,43 (3H, c), was 4.02 (3H, c), 4,22 (2H, user. c)5,07 (1H, t, J=5 Hz), 6,60 (1H, m), 6,69 (1H, c), to 6.80 (1H, d, J=16 Hz), 6,93 (1H, d, J=9 Hz), a 7.1 to 7.6 (5H, m), 8,16 (1H, d, J=2 Hz), 8,23 (1H, c), 8,54 (1H, user. c).

Example 24

Obtain N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5-[(3,4-acid)sulfonyl]-5H-pyrrolo[3,2-d]pyrimidine-4-amine

The hydrochloride of N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine (150 mg) was dissolved in N,N-dimethylformamide (1.5 ml) and potassium carbonate (102 mg) and (3,4-acid)sulphonylchloride (96,9 mg) was sequentially added under ice cooling. The mixture was stirred under ice cooling for 2 h and at room temperature for 1 h the Mixture was diluted with ethyl acetate (50 ml) and washed twice with water (30 ml). The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by chromatography on a column of silica gel (eluent: hexane:ethyl acetate=80:20→0:100) to obtain the specified title compound (95 mg) in powder form.

1H-NMR (CDCl3) δ: 3,68 (3H, c), 3,86 (3H, c), 5,16 (2H, c), 6,76 (1H, d, J=4 Hz), PC 6.82 (1H, d, J=9 Hz), 6,97 (1H, d, J=9 Hz), 7,02 (1H, m)and 7.1 to 7.4 (5H, m), 7,55 (1H, DD, J=9 Hz, 3 Hz), 7,79 (1H, d, J=4 Hz), 7,94 (1H, d, J=3 Hz), charged 8.52 (1H, c), 9,39 (1H, user. c).

Example 25

Getting 5-{[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]methyl}-2-ethylformate

(A) receiving 5-[(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)methyl]-2-ethylformate

To a suspension of 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (500 mg) in N,N-dimethylformamide (6.5 ml) was added potassium carbonate (541 mg) under ice cooling and the mixture was stirred for 15 minutes while heating the mixture to room temperature. Was added to the reaction mixture of 5-(chloromethyl)-2-ethylfuran (737 mg) and the mixture was stirred at room temperature for 16 hours, the Reaction mixture was diluted with water (20 ml) and was extracted with mixed solvent (40 ml×3) ethyl acetate-tetrahydrofuran (1/1). The organic layer was washed with saturated salt solution (20 ml×3) and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel (silica gel, eluent: hexane/ethyl acetate=80/20→10/90). The target fraction was concentrated under reduced pressure and dried to obtain specified in the title compound (825 mg) as a pale yellow solid.

1H-NMR (CDCl3) δ of 1.37 (3H, t, J=7.2 Hz), 4,36 (2H, q, J=7.2 Hz), of 5.75 (2H, c), 6,30 (1H, DDD, J=0,9, 2,1, 2.7 Hz), to 6.80 (1H, t, J=3,9 Hz), 7,10 (1H, t, J=3.3 Hz), 7,63 (1H, DD, J=2.7, and 3.3 Hz), 8,73 (1H, d, J=3,9 Hz).

(ii) Obtain 5-{[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]methyl}-2-ethylformate

To a solution of 5-[(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)methyl]-2-ethylformate (200 mg) in 1-methyl-2-pyrrolidone (1.3 ml) was added 3-chloro-4-[(3-terbisil)oxy]aniline (247 m is) and the mixture was heated to 140°C and was stirred for 2 hours The reaction mixture was allowed to cool to room temperature, diluted with 5% aqueous sodium hydrogen carbonate solution (20 ml) and was extracted with ethyl acetate (20 ml×3). The organic layer was washed with saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel (silica gel, eluent: ethyl acetate/methanol=10/0→8/2). The target fraction was concentrated under reduced pressure and dried to obtain specified in the title compound (307 mg) as a pale yellow solid.

1H-NMR (CDCl3) δ of 1.34 (3H, t, J=7.2 Hz), to 4.38 (2H, q, J=7.2 Hz), 5,14 (2H, c), 5,49 (2H, c), of 6.45 (1H, d, J=3,4 Hz), 6,63 (1H, d, J=3.0 Hz), 6,94 (1H, d, J=8,8 Hz), 7,03 (1H, d, J=9.6 Hz), 7,26-7,38 (6H, m), the 7.43 (1H, DD, J=2,6, 8,8 Hz), the 7.65 (1H, d, J=3.0 Hz), and 8.50 (1H, c).

Example 26

Getting 5-{[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]methyl}-2-frankenboob acid

To a solution of 5-{[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]methyl}-2-ethylformate (280 mg) in a mixed solvent of tetrahydrofuran (1,34 ml) and ethanol (1,34 ml) was administered 1H. an aqueous solution of sodium hydroxide (1,34 ml) and the mixture was stirred at room temperature for 14 hours was Added to the reaction mixture 1H. hydrochloric acid (1,34 ml) and water (0 ml) and the mixture was stirred at room temperature for 30 minutes The precipitate was separated by filtration, washed with water (10 ml×3) and diisopropyl ether (10 ml×3) and dried under reduced pressure (80°C) obtaining specified in the title compound (178 mg) as a white powder.

1H-NMR (DMSO-d6) ∆ 5,24 (2H, c), of 5.89 (2H, c), 6,37 (1H, d, J=3.3 Hz), is 6.54 (1H, d, J=2.7 Hz), 7,10 (1H, d, J=3.3 Hz), 7,21 (2H, d, J=9.0 Hz), 7,32 (2H, t, J=6.6 Hz), of 7.48 (2H, t, J=8.1 Hz), 7,73 (2H, d, J=9.6 Hz), 8,29 (1H, c), to 8.57 (1H, user. c).

Example 27

Obtain N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5-{4-[(CIS-3,5-dimethylpiperazine-1-yl)carbonyl]benzyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

To a solution of 4-{[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]methyl}benzoic acid (120 mg) in N,N-dimethylformamide (2.4 ml) was added CIS-2,6-dimethylpiperazine (95 mg) and 1H-1,2,3-benzotriazol-1-ol (65 mg) and the mixture was stirred at room temperature for 15 minutes was Added the hydrochloride of N-[3-(dimethylamino)propyl]-N'-ethylcarbodiimide (92 mg) and triethylamine (0.2 ml) and the mixture was stirred at room temperature for 12 hours, the Reaction mixture was diluted with water (20 ml) and was extracted with ethyl acetate (25 ml×3). The organic layer was washed with saturated salt solution (20 ml×3) and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel (basically the silica gel, eluent: ethyl acetate/methanol=10/0→9/1). The target fraction was concentrated under reduced pressure. To the residue was added a mixture of chloroform-diisopropyl ether (3/7), the precipitate was separated by filtration and dried under reduced pressure to obtain specified in the title compound (85 mg) as white powdery crystals.

1H-NMR (CDCl3) δ of 1.13 (6H, d, J=6.6 Hz), of 1.66 (4H, user. c)2,69 (2H, usher.), to 3.41 (1H, userd, J=6.6 Hz), 4,60 (1H, userd, J=13.5 Hz), to 5.08 (2H, c)to 5.56 (2H, c), 6,28 (1H, c), of 6.68 (1H, DD, J=2.1 a, 5,4 Hz), PC 6.82 (1H, d, J=9.3 Hz), 7,00 (2H, dt, J=2,1, to 8.7 Hz), 7,15-7,21 (4H, m), 7,25 (1H, d, J=2.4 Hz), 7,30-7,38 (4H, m), of 7.48 (2H, d, J=8,4 Hz), 8,48 (1H, c).

Example 28

Obtaining N-[3-chloro-4-(pyridine-2-ylethoxy)phenyl]-5H-pyrrolo[3,2-d]pyrimidine-4-amine

To a solution of 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (63 mg) in 1-methyl-2-pyrrolidone (0.8 ml) was added 3-chloro-4-(pyridine-2-ylethoxy)aniline (149 mg), the mixture was heated to 140°C and was stirred for 2 h the Reaction mixture was allowed to cool to room temperature, diluted with 5% aqueous sodium hydrogen carbonate solution (20 ml) and was extracted with a mixed solvent (25 ml×3) ethyl acetate-tetrahydrofuran (1/1). The organic layer was washed with saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel (basically the silica gel, eluent: ethyl acetate/methanol=10/0→8/2). The target fraction was concentrated under reduced pressure. To the residue was added a mixture of chloroform-diisopropyl ether (1/9), the precipitate was separated by filtration and dried under reduced pressure to obtain specified in the title compound (112 mg) as pale yellow powdery crystals.

1H-NMR (DMSO-d6) δ 5,27 (2H, c), 6,48 (1H, d, J=2.4 Hz), 7,25 (1H, d, J=8.7 Hz), 7,37 (1H, DD, J=5,1, 7.5 Hz), 7,55-of 7.60 (2H, m), 7,66 (1H, c), 7,89 (1H, t, J=7.5 Hz), to 8.20 (1H, DD, J=1.5 and 2.4 Hz), 8,35 (1H, d, J=1.5 Hz), at 8.60 (1H, DD, J=0,6, 4,8 Hz), the 9.25 (1H, c), 12,78 (1H, c).

Example 29

Getting 5-[(4-{[3-chloro-4-(pyridine-2-ylethoxy)phenyl]amino}-5H-pyrrolo[3,2-d]pyrimidine-5-yl)methyl]-2-ethylformate

To a solution of 5-[(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)methyl]-2-ethylformate (300 mg) in 1-methyl-2-pyrrolidone (2.0 ml) was added 3-chloro-4-(pyridine-2-ylethoxy)aniline (360 mg) and the mixture was heated to 140°C and stirred for 1.5 hours the Reaction mixture was allowed to cool to room temperature, diluted with 5% aqueous sodium hydrogen carbonate solution (30 ml) and was extracted with a mixed solvent (45 ml×3) ethyl acetate-tetrahydrofuran (1/1). The organic layer was washed with saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel basic silica gel, eluent: ethyl acetate/methanol=10/0→8/2). The target fraction was concentrated under reduced pressure. To the residue was added a mixture of chloroform-diisopropyl ether (1/9), the precipitate was separated by filtration and dried under reduced pressure to obtain specified in the title compound (440 mg) as pale yellow powdery crystals.

1H-NMR (CDCl3) δ of 1.37 (3H, t, J=7.2 Hz), 4,36 (2H, q, J=7.2 Hz), 5,33 (2H, c), 5,91 (2H, c), to 6.39 (1H, d, J=3,4 Hz), to 6.57 (1H, d, J=2.6 Hz), 7,12 (1H, d, J=3,4 Hz), 7.23 percent (1H, d, J=9.0 Hz), the 7.43 (1H, DD, J=4,8, 7,8 Hz), to 7.50 (1H, DD, J=2,2, 9,2 Hz), to 7.61 (1H, d, J=7.8 Hz), of 7.75 (2H, c), of 7.90 (1H, dt, J=1,2, 7,8 Hz)to 8.14 (1H, d, J=4,8 Hz), 8,30 (1H, c), 8,55 (1H, user. c).

Example 30

Getting 5-[(4-{[3-chloro-4-(pyridine-2-ylethoxy)phenyl]amino}-5H-pyrrolo[3,2-d]pyrimidine-5-yl)methyl]-2-frankenboob acid

To a solution of 5-[(4-{[3-chloro-4-(pyridine-2-ylethoxy)phenyl]amino}-5H-pyrrolo[3,2-d]pyrimidine-5-yl)methyl]-2-ethylformate (440 mg) in a mixed solvent of tetrahydrofuran (2.0 ml) and ethanol (2.0 ml) was added 1N. an aqueous solution of sodium hydroxide (2.0 ml) and the mixture was stirred at room temperature for 5 hours was Added to the reaction mixture 1H. hydrochloric acid (2.0 ml) and water (25 ml) and the mixture was stirred at room temperature for 30 minutes the precipitate was separated by filtration, washed with water (10 ml×3) and diisopropyl ether (10 ml×3) and dried at below the nom pressure (80°C) obtaining specified in the title compound (310 mg) as white powdery crystals.

1H-NMR (DMSO-d6) δ 5,27 (2H, c), 5,88 (2H, c), 6.35mm (1H, d, J=3,4 Hz), 6,53 (1H, d, J=2.6 Hz), was 7.08 (1H, d, J=3,4 Hz), 7,20 (1H, d, J=9.0 Hz), 7,37 (1H, DD, J=4,8,7,8 Hz), 7,47 (1H, DD, J=2,2, 9,2 Hz), 7,58 (1H, d, J=7,8 Hz), 7,73 (2H, c), 7,88 (1H, t, J=1,2, 7,8 Hz), of 8.27 (1H, c), 8,53 (1H, user. c)8,59 (1H, d, J=4,8 Hz).

Example 31

Getting 2-(3,5-dichlorophenoxy)-5-(5H-pyrrolo[3,2-d]pyrimidine-4-ylamino)ethylbenzoic

To a solution of 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (61 mg) in 1-methyl-2-pyrrolidone (0.8 ml) was added 5-amino-2-(3,5-dichlorophenoxy)ethylbenzoic (186 mg) and the mixture was heated to 140°C and stirred for 2.5 hours the Reaction mixture was allowed to cool to room temperature, diluted with 5% aqueous sodium hydrogen carbonate solution (20 ml) and was extracted with a mixed solvent (25 ml×3) ethyl acetate-tetrahydrofuran (1/1). The organic layer was washed with saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel (basic silica gel, eluent: hexane/ethyl acetate=8/2→0/10). The target fraction was concentrated under reduced pressure. Ethyl acetate was added to the residue, the precipitate was separated by filtration and dried under reduced pressure to obtain specified in the title compound (149 mg) as pale yellow powdery crystals.

1H-NMR (DMSO-d6 ) δ of 1.10 (3H, t, J=7.2 Hz), 4,18 (2H, q, J=7.2 Hz), of 6.52 (1H, d, J=2,8 Hz), 6,90 (2H, t, J=3.0 Hz), 7,28 (1H, DD, J=1,8, 2,8 Hz), 7,33 (1H, DD, J=8,8 Hz), 7,71 (1H, d, J=2,8 Hz), at 8.36 (2H, d, J=8,8 Hz), 8,39 (1H, d, J=1,8 Hz), 9,60 (1H, c), of 11.15 (1H, c).

Example 32

Getting 2-(3,5-dichlorophenoxy)-5-(5H-pyrrolo[3,2-d]pyrimidine-4-ylamino)benzoic acid

To a solution of 2-(3,5-dichlorophenoxy)-5-(5H-pyrrolo[3,2-d]pyrimidine-4-ylamino)ethylbenzoic (100 mg) in a mixed solvent of tetrahydrofuran (0.68 ml) and ethanol (0.68 ml) was added 1N. an aqueous solution of sodium hydroxide (0.68 ml) and the mixture was stirred at room temperature for 16 hours was Added to the reaction mixture 1H. hydrochloric acid (0.68 ml) and water (5 ml) and the mixture was stirred at room temperature for 30 minutes the precipitate was separated by filtration, washed with water (10 ml×3) and diisopropyl ether(10 ml×3) and dried under reduced pressure (80°C) obtaining specified in the title compound (76 mg) as white powdery crystals.

1H-NMR (DMSO-d6) δ of 6.52 (1H, d, J=1.2 Hz), 6,90 (2H, t, J=1.2 Hz), 7,28 (2H, dt, J=3,0, 5,1 Hz), 7,71 (1H, t, J=2.7 Hz), 8,29 (1H, DD, J=2.7, and 8.7 Hz), of 8.37 (1H, d, J=2.7 Hz), 8,40 (1H, d, J=1.2 Hz), 9,59 (1H, c), 11,18 (1H user. c).

Example 33

Obtain N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5-ethyl-5H-pyrrolo[3,2-d]pyrimidine-4-amine

(i) Obtaining 4-chloro-5-ethyl-5H-pyrrolo[3,2-d]pyrimidine

To suspend and 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (200 mg) in N,N-dimethylformamide (1.3 ml) was added potassium carbonate (269 mg) under ice cooling and the mixture was stirred, allowing to warm to room temperature for 15 min Iodate (305 mg) was added to the reaction mixture and the mixture was stirred at room temperature for 3 hours, the Reaction mixture was diluted with water (20 ml) and was extracted with ethyl acetate (30 ml×3). The organic layer was washed with saturated salt solution (20 ml×3) and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel (silica gel, eluent: hexane/ethyl acetate=80/20→10/90). The target fraction was concentrated under reduced pressure and dried to obtain specified in the title compound (187 mg) as a pale yellow solid.

1H-NMR (CDCl3) δ of 1.52 (3H, t, J=7.2 Hz), 4,55 (2H, q, J=7.2 Hz), was 6.73 (1H, d, J=3.2 Hz), 7,51 (1H, d, J=3.2 Hz), to 8.70 (1H, c).

(ii) Obtaining N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5-ethyl-5H-pyrrolo[3,2-d]pyrimidine-4-amine

To a solution of 4-chloro-5-ethyl-5H-pyrrolo[3,2-d]pyrimidine (85 mg) in 1-methyl-2-pyrrolidone (0,94 ml) was added 3-chloro-4-[(3-terbisil)oxy]aniline (177 mg). Specified in the title compound (98 mg) was obtained as a pale-purple powder crystals by the interaction is similar to the method of example 29.

1H-NMR (CDCl3) δ of 1.56 (3H, t, J=7.4 Hz), to 4.33 (2H, q, J=7.4 Hz), 5,15 (2H, c), 6,51 (1H, user. c)to 6.58 (1H, d, J=3.0 Hz), 6,72 (2H, c), to 6.95 (1H, d, J=8.7 Hz), 7,02 (1H, m), 7,21 (1H, d, J=8.5 Hz), 7,25 (1H, d, J=3.0 Hz), 733-7,40 (2H, m), 7,60 (1H, d, J=2.5 Hz), 8,49 (1H, user. c).

Example 34

Getting 5-ethyl-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

To a solution of 4-chloro-5-ethyl-5H-pyrrolo[3,2-d]pyrimidine (85 mg) in 1-methyl-2-pyrrolidone (0,94 ml) was added 3-methyl-4-[(6-methylpyridin-3-yl)oxy]aniline (150 mg). Specified in the title compound (67 mg) was obtained as white powder crystals by the interaction is similar to the method of example 29.

1H-NMR (CDCl3) δ of 1.57 (3H, t, J=7,4 Hz in), 2.25 (3H, c), of 2.53 (3H, c), of 4.35 (2H, q, J=7.4 Hz), to 6.58 (1H, d, J=3.0 Hz), to 6.67 (1H, user. c)6,89 (1H, d, J=8.7 Hz), was 7.08 (1H, d, J=8.5 Hz), 7,13 (1H, DD, J=3,0, to 8.7 Hz), 7,25 (1H, d, J=3.0 Hz), 7,34 (1H, DD, J=2,6, and 8.7 Hz), 7,42 (1H, d, J=2.5 Hz), 8,23 (1H, d, 1H, J=2,5 Hz)and 8.50 (1H, c).

Example 35

Obtain N-benzyl-N'-[3-(5H-pyrrolo[3,2-d]pyrimidine-4-ylamino)phenyl]urea

To a solution of 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (100 mg) in 1-methyl-2-pyrrolidone (1.3 ml) was added N-(3-AMINOPHENYL)-N'-benzyladenine (220 mg), the mixture was heated to 140°C and stirred for 1.5 hours the Reaction mixture was allowed to cool to room temperature, diluted with 5% aqueous sodium hydrogen carbonate solution (20 ml) and was extracted with mixed solvent (30 ml×3) ethyl acetate-tetrahydrofuran (1/1). The organic layer was washed with saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated the ri reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel (basic silica gel, eluent: ethyl acetate/methanol=100/0→85/15). The target fraction was concentrated under reduced pressure. To the residue was added ethyl acetate, the precipitate was separated by filtration and dried under reduced pressure to obtain specified in the title compound (97 mg) as pale yellow powdery crystals.

1H-NMR (DMSO-d6) δ 4,32 (2H, d, J=5.8 Hz), 6,47 (1H, c), 6,63 (1H, t, J=5.8 Hz), 7,02 (1H, d, J=8,4 Hz), 7,16-to 7.32 (6H, m), a 7.62 (2H, d, J=8,4 Hz), 7,98 (1H, c), with 8.33 (1H, c), 8,63 (1H, c)to 9.15 (1H, c), 11,22 (1H, c).

Example 36

Getting 4-{[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]methyl}-N-(2-hydroxyethyl)benzamide

To a solution of 4-{[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]methyl}benzoic acid (126 mg) in N,N-dimethylformamide (1.2 ml) was added the hydrochloride of N-[3-(dimethylamino)propyl]-N'-ethylcarbodiimide (72 mg) and 1-hydroxypyrrolidine-2,5-dione (43 mg) and the mixture was stirred at room temperature within 3 hours To the obtained reaction mixture was added dropwise a solution of 2-aminoethanol (23 mg) in a mixed solvent of N,N-dimethylformamide (1.2 ml) and 10% aqueous sodium hydrogen carbonate (1.2 ml) and the mixture was stirred at room temperature for 48 hours the Reaction mixture was diluted with water (25 ml) and was extracted with ethyl acetate (25 ml×3). The organic layer was washed with saturated salt solution (5 ml×3) and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel (basic silica gel, eluent: ethyl acetate/methanol=10/0→8/2). The target fraction was concentrated under reduced pressure. To the residue was added a mixture of chloroform-diisopropyl ether (1/4), the precipitate was separated by filtration and dried under reduced pressure to obtain specified in the title compound (105 mg) as white powdery crystals.

1H-NMR (DMSO-d6) δ is 3.27 (2H, t, J=5,9 Hz), 3,41-of 3.48 (2H, m), and 4.68 (1H, t, J=5,9 Hz), to 5.21 (2H, c), of 5.84 (2H, c), 6,56 (1H, d, J=3.0 Hz), 7,06 (2H, d, J=8.1 Hz), was 7.08 (2H, t, J=7.5 Hz), 7,27-to 7.35 (3H, m), 7,46 (1H, dt, J=5,8 and 8.1 Hz), to 7.64 (1H, d, J=2.5 Hz), 7,73 (2H, d, J=8,3 Hz), 7,82 (1H, d, J=3.0 Hz), of 8.27 (2H, c), with 8.33 (1H, t, J=5.4 Hz).

Example 37

Obtaining N-(3-amino-3-oxopropyl)-4-{[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]methyl}benzamide

Specified in the title compound (83 mg) was obtained as white powder crystals by the interaction is similar to the method of example 27 using 4-{[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]methyl}benzoic acid (120 mg), and hydrochloride of β-alaninemia (45 mg).

1H-NMR (DMSO-d6) δ to 2.29 (1H, t, J=7.2 Hz), 3,37-of 3.42 (4H, m), a total of 5.21 (2H, c), of 5.83 (2H, c), 6,56 (1H, d, J=3.3 Hz), to 6.80 (1H, user. c)7,06 (2H, d, J=8,3 Hz), 7,18 (2H, t, J=9.0 Hz), 7,29-7,34 (4H m), 7,46 (1H, dt, J=5,8, 7.9 Hz), 7,63 (1H, d, J=2.4 Hz), 7,71 (2H, d, J=8,3 Hz), 7,81 (1H, d, J=3.2 Hz), compared to 8.26 (1H, d, J=3.3 Hz), 8,40 (1H, t, J=5.7 Hz).

Example 38

Obtain N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5-(2-ethoxyethyl)-5H-pyrrolo[3,2-d]pyrimidine-4-amine

(i) Obtaining 4-chloro-5-(2-ethoxyethyl)-5H-pyrrolo[3,2-d]pyrimidine

To a suspension of 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (500 mg) in N,N-dimethylformamide (4.5 ml) was added cesium carbonate (1324 mg) under ice cooling and the mixture was stirred, allowing to warm to room temperature for 15 minutes 1-Bromo-2-ethoxyethane (1016 mg) was added to the reaction mixture and the mixture was stirred at room temperature for 14 hours, the Reaction mixture was diluted with water (100 ml) and was extracted with ethyl acetate (120 ml×3). The organic layer was washed with saturated salt solution (100 ml×3) and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel (silica gel, eluent: hexane/ethyl acetate=85/15→20/80). The target fraction was concentrated under reduced pressure and dried to obtain specified in the title compound (697 mg) as a pale yellow oil.

1H-NMR (CDCl3) δ of 1.13 (3H, t, J=6.9 Hz), of 3.43 (2H, q, J=6.9 Hz), of 3.78 (2H, t, J=5,1 Hz), of 4.67 (2H, t, J=5,1 Hz), of 6.71 (1H, d, J=3.0 Hz), to 7.59 (1H, d, J=3.0 Hz), to 8.70 (1H, c).

(ii) Obtaining N-{3-chloro-4-[(3-terbisil)oxy]the dryer is l}-5-(2-ethoxyethyl)-5H-pyrrolo[3,2-d]pyrimidine-4-amine

To a solution of 4-chloro-5-(2-ethoxyethyl)-5H-pyrrolo[3,2-d]pyrimidine (90 mg) in 1-methyl-2-pyrrolidone (0.7 ml) was added 3-chloro-4-[(3-terbisil)oxy]aniline (151 mg), the mixture was heated to 140°C and was stirred for 7 hours the Reaction mixture was allowed to cool to room temperature. The reaction mixture was diluted with 5% aqueous sodium hydrogen carbonate solution (20 ml) and was extracted with ethyl acetate (25 ml×3). The organic layer was washed with saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel (basic silica gel, eluent: ethyl acetate/methanol=10/0 → 8/2). The target fraction was concentrated under reduced pressure. The residue was recrystallized from diisopropyl ether, separated by filtration and dried under reduced pressure to obtain specified in the title compound (90 mg) as pale yellow needle crystals.

1H-NMR (CDCl3) δ 1,22 (3H, t, J=7.0 Hz), 3,63 (2H, q, J=7.0 Hz), 3,90 (2H, t, J=4.4 Hz), 4,50 (2H, t, J=4.4 Hz), 5,13 (2H, c), is 6.61 (1H, d, J=3.2 Hz), 6,94 (1H, d, J=8,9 Hz), 7,01 (1H, t, J=8.1 Hz), 7,17-of 7.25 (3H, m), 7,35 (1H, dt, J=5,6, 7,9 Hz), 7,47 (1H, DD, J=1,3, and 8.9 Hz), to 7.64 (1H, d, J=2.6 Hz), 8,48 (1H, c), 8,79 (1H, c).

Example 39

Obtain N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5-methyl-5H-pyrrolo[3,2-d]pyrimidine-4-amine

(i) Obtaining 4-chloro-5-methyl-5H-Pierre is lo[3,2-d]pyrimidine

To a suspension of 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (320 mg) in N,N-dimethylformamide (2.0 ml) was added potassium carbonate (452 mg) under ice cooling and the mixture was stirred, allowing to warm to room temperature for 15 min Itmean (444 mg) was added to the reaction mixture and the mixture was stirred at room temperature for 3 hours, the Reaction mixture was diluted with water (25 ml) and was extracted with ethyl acetate (30 ml×3). The organic layer was washed with saturated salt solution (20 ml×3) and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel (silica gel, eluent: hexane/ethyl acetate=80/20→10/90). The target fraction was concentrated under reduced pressure and dried to obtain specified in the title compound (325 mg) as a pale yellow solid.

1H-NMR (CDCl3) δ 4,16 (3H, c)6,70 (1H, d, J=3,9 Hz), 7,42 (1H, d, J=3,9 Hz), 8,69 (1H, c).

(ii) Obtaining N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5-methyl-5H-pyrrolo[3,2-d]pyrimidine-4-amine

To a solution of 4-chloro-5-methyl-5H-pyrrolo[3,2-d]pyrimidine (100 mg) in 1-methyl-2-pyrrolidone (1.0 ml) was added 3-chloro-4-[(3-terbisil)oxy]aniline (225 mg), the mixture was heated to 140°C and stirred for 1.5 hours the Reaction mixture was allowed to cool to room temperature, diluted with 5% aqueous sodium hydrogen carbonate solution (25 ml) and the ex who was regionali with ethyl acetate (30 ml×3). The organic layer was washed with saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel (eluent: hexane/ethyl acetate=95/5→0/100). The target fraction was concentrated under reduced pressure. The residue was recrystallized from a mixed solvent of diisopropyl ether and chloroform, separated by filtration and dried under reduced pressure to obtain specified in the title compound (121 mg) as a pale-yellow powder crystals.

1H-NMR (DMSO-d6) δ 4,14 (3H, c), of 5.24 (2H, c), 6.42 per (1H, d, J=3.0 Hz), 7,16-of 7.23 (2H, m), 7,29-7,34 (2H, m), 7,44-7,56 (3H, m), 7,78 (1H, d, J=2.4 Hz), 8,24 (1H, c), at 8.36 (1H, c).

Example 40

Getting 5-methyl-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

To a solution of 4-chloro-5-methyl-5H-pyrrolo[3,2-d]pyrimidine (100 mg) in 1-methyl-2-pyrrolidone (1.0 ml) was added 3-methyl-4-[(6-methylpyridin-3-yl)oxy]aniline (192 mg). Specified in the title compound (106 mg) was obtained as white powder crystals by the interaction is similar to the method of example 39 (ii).

1H-NMR (DMSO-d6) δ 2,17 (3H, c), is 2.44 (3H, c), is 4.15 (3H, c), to 6.43 (1H, DD, J=0,9, 3.0 Hz), 6,94 (1H, d, J=8,4 Hz), 7,18 (1H, DD, J=3,0, 8,4 Hz), 7,24 (1H, d, J=8.7 Hz), 7,51 (1H, d, J=8.7 Hz), 7,56 (1H, d, J=3.0 Hz), 8.17 and (1H, d, J=3.0 Hz), of 8.25 (1H, d, J0,9 Hz), to 8.40 (1H, c), 8,63 (1H, c).

Example 41

Getting 2-[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethanol

(i) Obtaining 5-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-4-chloro-5H-pyrrolo[3,2-d]pyrimidine

To a suspension of 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (307 mg) in N,N-dimethylformamide (2.0 ml) was added cesium carbonate (977 mg) under ice cooling and the mixture was stirred, allowing to warm to room temperature over 15 minutes To the reaction mixture was added tert-butyl(2-iodoxy)dimethylsilane (839 mg) and the mixture was stirred at room temperature for 16 hours, the Reaction mixture was diluted with water (20 ml) and was extracted with ethyl acetate (30 ml×3). The organic layer was washed with saturated salt solution (30 ml×3) and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel (silica gel, eluent: hexane/ethyl acetate=85/15→10/90). The target fraction was concentrated under reduced pressure and dried to obtain specified in the connection header (591 mg) as a white solid.

1H-NMR (DMSO-d6) δ of 0.95 (9H, c), 4,10 (2H, t, J=5,2 Hz), was 4.76 (2H, t, J=5,2 Hz), 6.87 in (1H, d, J=3.0 Hz), EUR 7.57 (1H, d, J=3.0 Hz), cent to 8.85 (1H, c).

(ii) Obtaining 2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethanol

To a solution of 5-(2-{[tert-butyl(dimethyl)Seeley is]oxy}ethyl)-4-chloro-5H-pyrrolo[3,2-d]pyrimidine (560 mg) in tetrahydrofuran (1.7 ml) was added tetrabutylammonium (1M tertrahydrofuran ring solution) (2,69 ml) under ice cooling and the mixture was stirred for 4 h The reaction mixture was diluted with water (20 ml) and was extracted with ethyl acetate (30 ml×3). The organic layer was washed with saturated salt solution (30 ml×3) and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel (silica gel, eluent: ethyl acetate/methanol=10/0→9/1). The target fraction was concentrated under reduced pressure and dried to obtain specified in the title compound (391 mg) as a white solid.

1H-NMR (CDCl3) δ 2,13 (2H, TD, J=6,3, and 12.6 Hz), of 4.66 (2H, t, J=6.3 Hz), 6,72 (1H, d, J=3.0 Hz), EUR 7.57 (1H, d, J=3.0 Hz), to 8.70 (1H, c).

(iii) Obtaining 2-[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethanol

To a solution of 2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethanol (130 mg) in 1-methyl-2-pyrrolidone (1.3 ml) was added 3-chloro-4-[(3-terbisil)oxy]aniline (193 mg) and the reaction mixture was stirred at 120°C for 2 h the Reaction mixture was allowed to cool to room temperature and added to it in ethyl acetate (20 ml). The precipitate was recrystallized from a mixed solvent of hexane-methanol (3/7), was separated by filtration and dried under reduced pressure to obtain specified in the title compound (206 mg) as pale purple crystals.

1H-NMR (DMSO-d6) δ 3,86 (2H, t, J=4.3 Hz), of 4.54 (2H, m), of 5.24 (2H, c), 6,23 (1H, user. c)6,53 (1, d, J=3.2 Hz), 7,18 (1H, dt, J=2,6, 8.1 Hz), 7,25 (1H, d, J=9.0 Hz), 7,29-7,34 (2H, m), 7,43-7,51 (2H, m), of 7.70 (1H, d, J=3.2 Hz), 7,78 (1H, d, J=2.6 Hz), of 8.37 (1H, user. c)9,82 (1H, user. c).

Example 42

Obtain N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5-propyl-5H-pyrrolo[3,2-d]pyrimidine-4-amine

(i) Obtaining 4-chloro-5-propyl-5H-pyrrolo[3,2-d]pyrimidine

To a suspension of 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (150 mg) in N,N-dimethylformamide (1.6 ml) was added cesium carbonate (798 mg) under ice cooling and the mixture was stirred, allowing to warm to room temperature over 15 minutes To the reaction mixture were added 1-bromopropane (301 mg) and the mixture was stirred at room temperature for 15 hours, the Reaction mixture was diluted with water (20 ml) and was extracted with ethyl acetate (30 ml×3). The organic layer was washed with saturated salt solution (30 ml×3) and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel (silica gel, eluent: hexane/ethyl acetate=90/10→20/80). The target fraction was concentrated under reduced pressure and dried to obtain specified in the title compound (161 mg) as a white solid.

1H-NMR (CDCl3) δ of 0.96 (3H, t, J=7.5 Hz), 1,86-to 1.98 (2H, m), of 4.44 (2H, t, J=7.5 Hz), was 6.73 (1H, t, J=3.3 Hz), of 7.48 (1H, d, J=3.3 Hz), to 8.70 (1H, c).

(ii) Obtaining N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5-impregnated is-5H-pyrrolo[3,2-d]pyrimidine-4-amine

To a solution of 4-chloro-5-propyl-5H-pyrrolo[3,2-d]pyrimidine (80 mg) in 1-methyl-2-pyrrolidone (0.8 ml) was added 3-chloro-4-[(3-terbisil)oxy]aniline (193 mg) and the reaction mixture was stirred at 120°C for 2 h the Reaction mixture was allowed to cool to room temperature, diluted with 5% aqueous sodium hydrogen carbonate solution (25 ml) and was extracted with ethyl acetate (30 ml×3). The organic layer was washed with saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel (eluent: ethyl acetate/methanol=100/0→95/5). The target fraction was concentrated under reduced pressure. To the residue was added a mixed solvent of diisopropyl ether and chloroform. The precipitate was separated by filtration and dried under reduced pressure to obtain specified in the title compound (96 mg) as a pale-purple powder.

1H-NMR (DMSO-d6) δ of 0.85 (3H, t, J=6.0 Hz), is 1.81 (2H, q, J=6.9 Hz), 4,42 (2H, t, J=6.9 Hz), 5,18 (2H, c), 6,47 (1H, DD, J=1,8, 3.0 Hz), 7,02 (1H, d, J=8.7 Hz), 7,06 (1H, d, J=2.4 Hz), 7,21-7,49 (4H, m), 7,71 (1H, d, J=the 2.4 Hz), to 7.77 (1H, user. c)8,07 (1H, user. c)to 8.34 (1H, d, J=2.1 Hz).

Example 43

Obtain N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5-isobutyl-5H-pyrrolo[3,2-d]pyrimidine-4-amine

(i) Obtaining 4-chloro-5-isobutyl-5H-pyrrolo[3,2-d]pyrimidine

To a suspension of 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (150 mg) in N,N-dimethylformamide (1.6 ml) was added cesium carbonate (478 mg) under ice cooling and the mixture was stirred, allowing to warm to room temperature over 15 minutes To the reaction mixture were added 1-bromo-2-methylpropan (336 mg) and the mixture was stirred at room temperature for 19 hours, the Reaction mixture was diluted with water (20 ml) and was extracted with ethyl acetate (30 ml×3). The organic layer was washed with saturated salt solution (30 ml×3) and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel (silica gel, eluent: hexane/ethyl acetate=90/10→20/80). The target fraction was concentrated under reduced pressure and dried to obtain specified in the title compound (210 mg) as a white solid.

1H-NMR (CDCl3) δ were 0.94 (6H, d, J=6.6 Hz), 2,14-of 2.27 (1H, m), 4.26 deaths (2H, d, J=7.5 Hz), 6,72 (1H, d, J=2.4 Hz), 7,46 (1H, d, J=2.4 Hz), to 8.70 (1H, c).

(ii) Obtaining N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5-isobutyl-5H-pyrrolo[3,2-d]pyrimidine-4-amine

Specified in the title compound (89 mg) was obtained as a pale-purple powder interaction, similar to the method of example 42 (ii)using a solution of 4-chloro-5-isobutyl-5H-pyrrolo[3,2-d]pyrimidine (90 mg) in 1-methyl-2-pyrrolidone (0.8 ml).

1H-NMR (DMSO-d6) δ of 0.83 (6H, d, J=6.3 Hz), of 2.08 (1H, m), 4,24 (2H, d, J=7.5 Hz), to 5.17 (2H, c), 6,47 (1H, d, J=2.7 Hz), 7,02 (2H, d, J=8.7 Hz), 7,22-7,29 (2H, m), 7,32 (1H, d, J=3.0 Hz), 7,40 (1H, dt, J=6,0, 8.1 Hz), 7,46 (1H, DD, J=2.7, and 9.0 Hz), 7,73 (1H, d, J=2.7 Hz) 7,79 (1H, c), of 8.09 (1H, user. c).

Example 44

Obtain N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5-(tetrahydrofuran-2-ylmethyl)-5H-pyrrolo[3,2-d]pyrimidine-4-amine

(i) Obtaining 4-chloro-5-(tetrahydrofuran-2-ylmethyl)-5H-pyrrolo[3,2-d]pyrimidine

To a suspension of 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (150 mg) in N,N-dimethylformamide (1.0 ml) was added cesium carbonate (478 mg) under ice cooling and the mixture was stirred, allowing to warm to room temperature over 15 minutes To the reaction mixture was added 2-(methyl bromide)tetrahydrofuran (242 mg) and the mixture was stirred at room temperature for 26 hours, the Reaction mixture was diluted with water (20 ml) and was extracted with ethyl acetate (30 ml×3). The organic layer was washed with saturated salt solution (30 ml×3) and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel (silica gel, eluent: hexane/ethyl acetate=90/10→20/80). The target fraction was concentrated under reduced pressure and dried to obtain specified in the title compound (200 mg) as a colourless oil.

1H-NMR (CDCl3) δ 1,47-of 1.64 (1H, m), 1.85 to 2,17 (3H, m), 3.75 to 3,90 (2H, m), 4,18-or 4.31 (1H, m), 4,42-a 4.53 (1H, m), 4,71 (1H, DD, J=3,4, 14.6 Hz), 6,74 (1H, d, J=3.0 Hz), 7,63 (1H, d, J=3.0 Hz), to 8.70 (1H, c).

(ii) Obtaining N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5-(tetrahydrofuran-2-ylmethyl)-H-pyrrolo[3,2-d]pyrimidine-4-amine

Specified in the title compound (139 mg) was obtained as a white powder interaction, similar to the method of example 42 (ii)using a solution of 4-chloro-5-(tetrahydrofuran-2-ylmethyl)-5H-pyrrolo[3,2-d]pyrimidine (200 mg) in 1-methyl-2-pyrrolidone (1.6 ml).

1H-NMR (DMSO-d6) δ 1.56 to of 1.65 (2H, m), of 1.78 and 1.80 (1H, m), 1,97-2,07 (1H, m), 3,70 (2H, m), 4,17-4,19 (1H, m), 4,43 (1H, DD, J=6,0, 15,0 Hz), of 4.67 (1H, d, J=13,8 Hz), to 5.21 (2H, c), 7,14 (1H, DD, J=8.1 Hz), 7,20 (1H, d, J=8,1 Hz), 7,27-of 7.48 (4H, m), to 7.61 (1H, d, J=2.1 Hz), 7,78 (1H, d, J=1.5 Hz), of 8.25 (1H, d, J=1.2 Hz), at 8.60 (1H, d, J=1.2 Hz), 9,03 (1H, c).

Example 45

Obtain 3-{[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]methyl}methylbenzoate

(i) Obtaining 3-[(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)methyl]methylbenzoate

To a suspension of 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (300 mg) in N,N-dimethylformamide (2.0 ml) was added cesium carbonate (955 mg) under ice cooling and the mixture was stirred, allowing to warm to room temperature over 15 minutes To the reaction mixture were added 3-(methyl bromide)methylbenzoate (671 mg) and the mixture was stirred at room temperature for 4 h, the Reaction mixture was diluted with water (40 ml) and was extracted with mixed solvent (40 ml×3) ethyl acetate-tetrahydrofuran (1/1). The organic layer was washed with saturated salt solution (120 ml×3) and dried over anhydrous magnesium sulfate. The solvent is evaporated at Pont the leaders introduce pressure and the obtained residue was subjected to chromatography on a column of silica gel (silica gel, eluent: hexane/ethyl acetate=80/20→10/90). The target fraction was concentrated under reduced pressure. To the residue was added a mixture of chloroform-diisopropyl ether (4/1), the precipitate was separated by filtration, washed and dried under reduced pressure to obtain specified in the title compound (319 mg) as pale brown powder.

1H-NMR (CDCl3) δ are 3.90 (3H, c), 5,77 (2H, c), PC 6.82 (1H, d, J=3,4 Hz), 7,19 (1H, DD, J=1,2, 7,8 Hz), 7,41 (1H, t, J=7.8 Hz), 7,54 (1H, d, J=3,4 Hz), 7,82 (1H, c), 7,98 (1H, dt, J=1,2, 7,8 Hz), 8,73 (1H, c).

(ii) Obtaining 3-{[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]methyl}methylbenzoate

To a solution of 3-[(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)methyl]methylbenzoate (670 mg) in 1-methyl-2-pyrrolidone (3.0 ml) was added 3-chloro-4-[(3-terbisil)oxy]aniline (549 mg) and the reaction mixture was stirred at 120°C for 1.5 hours the Reaction mixture was allowed to cool to room temperature, diluted with 5% aqueous sodium hydrogen carbonate solution (50 ml) and was extracted with ethyl acetate (50 ml×3). The organic layer was washed with saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel (basic silica gel, eluent: hexane/ethyl acetate=9/1→0/10). The target fraction was concentrated under reduced pressure and dried to obtain pointed to by the th in the connection header (1010 mg) as a yellow oil.

1H-NMR (CDCl3) δ 3,93 (3H, c), to 5.08 (2H, c), the ceiling of 5.60 (2H, c), to 6.39 (1H, c), to 6.67 (1H, d, J=3,4 Hz), PC 6.82 (1H, d, J=9,2 Hz), 7,01 (2H, DD, J=2,6, 8,8 Hz), 7,16-7,40 (3H, m), 7,56 (1H, t, J=7.8 Hz), 7,94 (1H, c), of 8.09 (1H, d, J=7.8 Hz), of 8.47 (1H, c).

Example 46

Obtain 3-{[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]methyl}benzoic acid

To a solution of 3-{[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]methyl}methylbenzoate (800 mg) in a mixed solvent of tetrahydrofuran (4.0 ml) and methanol (4.0 ml) was added 1N. an aqueous solution of sodium hydroxide (4.0 ml) and the mixture was stirred at room temperature for 12 hours was Added to the reaction mixture 1H. hydrochloric acid (4.0 ml) and water (15 ml) and the mixture was stirred at room temperature for 30 minutes the precipitate was separated by filtration, washed with water (10 ml×3) and diisopropyl ether (10 ml×3) and dried under reduced pressure (80°C) obtaining specified in the title compound (610 mg) as a white powder.

1H-NMR (DMSO-d6) δ to 5.21 (2H, c), 5,86 (2H, c), to 6.57 (1H, DD, J=1.5 and 3.3 Hz), 7,14-7,51 (8H, m), 7,58 (1H, DD, J=1.5 and 2.4 Hz), 7,69 (1H, c), 7,78 (1H, d, J=6.3 Hz), to 7.84 (1H, d, J=1,8 Hz), of 8.27 (1H, d, J=1.5 Hz), 8,30 (1H, c).

Example 47

Getting 5-(2-ethoxyethyl)-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

To a solution of 4-chloro-5-(2-this is setil)-5H-pyrrolo[3,2-d]pyrimidine (160 mg) in 1-methyl-2-pyrrolidone (1,4 ml) was added 3-methyl-4-[(6-methylpyridin-3-yl)oxy]aniline (228 mg) and the reaction mixture was stirred at 120°C for 2 hours The reaction mixture was allowed to cool to room temperature, diluted with 5% aqueous sodium hydrogen carbonate solution (25 ml) and was extracted with ethyl acetate (40 ml×3). The organic layer was washed with saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel (eluent: hexane/ethyl acetate=90/10→0/100). The target fraction was concentrated under reduced pressure and dried to obtain specified in the title compound (191 mg) as a colorless transparent oil.

1H-NMR (CDCl3) δ 1,25 (3H, dt, J=2,1, 7,2 Hz), and 2.14 (3H, c), 2,52 (3H, c), the 3.65 (2H, q, J=7.2 Hz), to 3.92 (2H, t, J=4.5 Hz), of 4.54 (2H, t, J=4.5 Hz), 6,62 (1H, d, J=3.0 Hz), 6,91 (1H, d, J=8,4 Hz), 7,11 (1H, DD, J=2.7, and and 8.4 Hz), 7,20 (1H, d, J=3.0 Hz), 7,40 (1H, DD, J=2.7, and an 8.4 Hz), 7,51 (1H, d, J=3.0 Hz), compared to 8.26 (1H, DD, J=0,6, 2.7 Hz), and 8.50 (1H, c), 8,84 (1H, user. c).

Example 48

Obtaining N-[3-chloro-4-(pyridine-2-ylethoxy)phenyl]-5-(2-ethoxyethyl)-5H-pyrrolo[3,2-d]pyrimidine-4-amine

To a solution of 4-chloro-5-(2-ethoxyethyl)-5H-pyrrolo[3,2-d]pyrimidine (160 mg) in 1-methyl-2-pyrrolidone (1,4 ml) was added 3-chloro-4-(pyridine-2-ylethoxy)aniline (250 mg). Specified in the title compound (160 mg) was obtained as pale-yellow needle-shaped crystals, the interaction is similar to the method of example 42 (ii).

1H-NMR (CDCl3) δ of 1.23 (3H, t, J=7.2 Hz), to 3.64 (2H, q, J=7,2 Hz), 3,91 (2H, t, J=7.2 Hz), 4,51 (2H, t, J=7.2 Hz), 5,27 (2H, c), 6,12 (1H, c), is 6.61 (1H, d, J=3.3 Hz), 6,97 (1H, d, J=8.7 Hz), 7,18 (1H, d, J=3.3 Hz), 7,42 (1H, DD, J=2.7, and 8.7 Hz), 7,66 (1H, c), of 7.69 (1H, d, J=2.1 Hz), 7,76 (1H, dt, J=1.5 and 8.7 Hz), 8,49 (1H, c), at 8.60 (1H, d, J=4.5 Hz), 8,81 (1H, c).

Example 49

Obtain N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5-(2-foradil)-5H-pyrrolo[3,2-d]pyrimidine-4-amine

(i) Obtaining 4-chloro-5-(2-foradil)-5H-pyrrolo[3,2-d]pyrimidine

To a suspension of 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (100 mg) in N,N-dimethylformamide (0.6 ml) was added cesium carbonate (281 mg) under ice cooling and the mixture was stirred, allowing to warm to room temperature over 15 minutes To the reaction mixture were added 1-bromo-2-foraten (124 mg) and the mixture was stirred at room temperature for 5 hours, the Reaction mixture was diluted with water (20 ml) and was extracted with ethyl acetate (20 ml×3). The organic layer was washed with saturated salt solution (20 ml×3) and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel (silica gel, eluent: hexane/ethyl acetate=90/10→0/10). The target fraction was concentrated under reduced pressure and dried to obtain specified in the title compound (110 mg) as a colorless transparent oil.

1H-NMR (CDCl3) δ with 4.64-4,69 (1H, m), 4.75 V-rate 4.79 (1H, m), 4,91 (2H, d, J=5,1 Hz), 6,77 (1H, DD, J=1,4, and 3.4 Hz), EUR 7.57 (1H,d, J=3,4 Hz), 8,73 (1H, c).

(ii) Obtaining N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5-(2-foradil)-5H-pyrrolo[3,2-d]pyrimidine-4-amine

Specified in the title compound (124 mg) was obtained as white powder crystals by the interaction is similar to the method of example 39 (ii)using a solution of 4-chloro-5-(2-foradil)-5H-pyrrolo[3,2-d]pyrimidine (110 mg) in 1-methyl-2-pyrrolidone (1.0 ml).

1H-NMR (CDCl3) δ with 4.65(2H, dt, J=4,0, 29.0 Hz), the 4.90(2H, dt, J=4,0, to 47.2 Hz), 5,14 (2H, c), of 6.65 (1H, d, J=3.0 Hz), 6,93 (1H, d, J=8,8 Hz),? 7.04 baby mortality (1H, d, J=8,8 Hz), 7,21-7,41 (6H, m), 7,55 (1H, c), 8,48 (1H, c).

Example 50

Obtain 3-{[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]methyl}-N-(2-hydroxyethyl)benzamide

Specified in the title compound (93 mg) was obtained as white powder crystals by the interaction is similar to the method of example 36 using 3-{[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]methyl}benzoic acid (126 mg).

1H-NMR (DMSO-d6) δ 3,26-of 3.48 (4H, m), 4,71 (1H, t, J=5.6 Hz), to 5.21 (2H, c), of 5.83 (2H, c), 6,55 (1H, d, J=2.6 Hz), 7,06-7,52 (7H, m), to 7.61-7,72 (4H, m), 7,80 (1H, d, J=3.2 Hz), compared to 8.26 (2H, c), 8,39 (1H, m).

Example 51

Obtain ethyl[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]acetate

(i) Obtaining ethyl(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)acetate

To suspe the Ziya 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (200 mg) in N,N-dimethylformamide (1.3 ml) was added cesium carbonate (615 mg) under ice cooling and the mixture was stirred, allowing to warm to room temperature over 15 minutes To the reaction mixture was added ethylbromoacetate (326 mg) and the mixture was stirred at room temperature for 2.5 hours, the Reaction mixture was diluted with water (20 ml) and was extracted with ethyl acetate (20 ml×3). The organic layer was washed with saturated salt solution (20 ml×3) and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel (silica gel, eluent: hexane/ethyl acetate=90/10→0/10). The target fraction was concentrated under reduced pressure and dried to obtain specified in the title compound (210 mg) as white powdery crystals.

1H-NMR (DMSO-d6) δ of 1.29 (3H, t, J=7.2 Hz), 4,27 (2H, q, J=7.2 Hz), to 5.21 (2H, c), to 6.80 (1H, d, J=3.3 Hz), was 7.45 (1H, d, J=3.3 Hz), total of 8.74 (1H, c).

(ii) Obtain ethyl[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]acetate

To a solution of ethyl(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)acetate (140 mg) in isopropyl alcohol (0.6 ml) was added 3-methyl-4-[(6-methylpyridin-3-yl)oxy]aniline (188 mg) and the mixture was stirred on an oil bath at 110°C for 2 h the Reaction mixture was allowed to cool to room temperature, diluted with 5% aqueous sodium hydrogen carbonate solution (20 ml) and was extracted with ethyl acetate (25 ml×3). The organic layer is washed and saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel (basic silica gel, eluent: ethyl acetate/methanol=10/0→9/1). The target fraction was concentrated under reduced pressure. Diisopropyl ether was added to the residue, the precipitate was separated by filtration and dried under reduced pressure to obtain specified in the title compound (210 mg) as white powdery crystals.

1H-NMR (CDCl3) δ is 1.35 (3H, t, J=7,0 Hz in), 2.25 (3H, c), of 2.53 (3H, c), of 4.35 (2H, q, J=7.0 Hz), 4,96 (2H, c), only 6.64 (1H, d, J=3,4 Hz), make 6.90 (1H, d, J=8,8 Hz), was 7.08 (1H, d, J=1,8 Hz), to 7.09 (1H, d, J=2.6 Hz), 7,22 (1H, d, J=3,4 Hz), 7,37 (1H, d, J=8,8 Hz), 7,44 (1H, d, J=2.6 Hz), 8,17 (1H, user. c), compared to 8.26 (1H, d, J=1,8 Hz), 8,53 (1H, c).

Example 52

Obtain [4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]acetic acid

Specified in the title compound (101 mg) was obtained as a white powder interaction, similar to the method of example 46, using ethyl[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]acetate (200 mg).

1H-NMR (DMSO-d6) δ 2,43 (3H, c), of 2.51 (3H, c), and 5.30 (2H, c), of 6.49 (1H, c), 6,92 (1H, d, J=8,8 Hz), 7,20-of 7.25 (2H, m), 7,37-7,44 (2H, m), a 7.62 (1H, c), 8,17 (1H, c), 8,31 (1H, c).

Example 53

Obtain 3-[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[,2-d]pyrimidine-5-yl]propan-1-ol

(i) Obtaining 5-(3-{[tert-butyl(dimethyl)silyl]oxy}propyl)-4-chloro-5H-pyrrolo[3,2-d]pyrimidine

To a suspension of 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (400 mg) in N,N-dimethylformamide (2.6 ml) was added cesium carbonate (957 mg) under ice cooling and the mixture was stirred, allowing to warm to room temperature over 15 minutes To the reaction mixture was added (3-bromopropane)(tert-butyl)dimethylsilane (979 mg) and the mixture was stirred at room temperature for 16 hours, the Reaction mixture was diluted with water (20 ml) and was extracted with ethyl acetate (30 ml×3). The organic layer was washed with saturated salt solution (30 ml×3) and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel (silica gel, eluent: hexane/ethyl acetate=85/15→10/90). The target fraction was concentrated under reduced pressure and dried to obtain specified in the title compound (630 mg) as a white solid.

1H-NMR (CDCl3) δ of 0.95 (9H, c), and 2.83 (2H, t, J=5,2 Hz), 4,10 (2H, t, J=5,2 Hz), was 4.76 (2H, t, J=5,2 Hz), 6.87 in (1H, d, J=2,8 Hz), 7,71 (1H, d, J=2,8 Hz), cent to 8.85 (1H, c).

(ii) Obtaining 3-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)propan-1-ol

Specified in the title compound (320 mg) was obtained as white powder crystals by the interaction is similar to the method of example 41 (ii)using 5-(3-{[tert-Buti is(dimethyl)silyl]oxy}propyl)-4-chloro-5H-pyrrolo[3,2-d]pyrimidine (600 mg).

1H-NMR (CDCl3) δ 2,13 (2H, dt, J=6,3, and 12.6 Hz), the 3.65 (2H, DD, J=6,3, 10,2 Hz), of 4.66 (2H, t, J=6.3 Hz), 6,72 (1H, d, J=3.0 Hz), EUR 7.57 (1H, d, J=3.0 Hz), to 8.70 (1H, c).

(iii) Obtaining 3-[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]propan-1-ol

Specified in the title compound (180 mg) was obtained as pale purple crystals the interaction is similar to the method of example 41 (iii)using 3-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)propan-1-ol (100 mg).

1H-NMR (DMSO-d6) δ to 1.98 (2H, t, J=6.0 Hz), 3,39 (2H, t, J=6.0 Hz), of 4.66 (2H, t, J=6.0 Hz), and 5.30 (2H,c), of 6.66 (1H, d, J=3.2 Hz), 7,19 (1H, dt, J=1,9, 8,3 Hz), 7,29-7,34 (3H, m), 7,44-7,52 (2H, m), 7,72 (1H, d, J=2,6 Hz), of 8.00 (1H, d, J=3.2 Hz), 8,66 (1H, c), becomes 9.97 (1H, c).

Example 54

Obtaining N-(2-hydroxyethyl)-2-[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ndimethylacetamide

Specified in the title compound (38 mg) was obtained as a white powder interaction, similar to the method of example 36 using [4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenylamino}-5H-pyrrolo[3,2-d]pyrimidine-5-yl)acetic acid (70 mg).

1H-NMR (DMSO-d6) δ 2,17 (3H, c), 2,43 (3H, c), 3,24 (2H, DD, J=5,6, 11.3 Hz), 3,47 (2H, DD, J=5,6, 11.3 Hz), a 4.86 (1H, t, J=5.3 Hz), 5,04 (2H, c), of 6.49 (1H, d, J=3.0 Hz), 6,97 (1H, d, J=8.5 Hz), to 7.15 (1H, DD, J=2,8, 8,5 Hz), 7,22 (1H, d, J=8.5 Hz), 7,54-EUR 7.57 (3H, m), 8,16 (1H, d, J=2.5 Hz), 8,30 (1H, c), 8,91 (1H, t, J=5.6 Hz), 10,10 (1H, c).

Example 55

(i) Obtaining 4-chloro-5-(4,4,4-trifloromethyl)-5H-pyrrolo[3,2-d]pyrimidine

To a suspension of 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (250 mg) in N,N-dimethylformamide (1.6 ml) was added cesium carbonate (675 mg) under ice cooling and the mixture was stirred, allowing to warm to room temperature over 15 minutes To the reaction mixture were added 4-bromo-1,1,1-triptorelin (466 mg) and the mixture was stirred at room temperature for 15 hours, the Reaction mixture was diluted with water (20 ml) and was extracted with ethyl acetate (20 ml×3). The organic layer was washed with saturated salt solution (20 ml×3) and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel (silica gel, eluent: hexane/ethyl acetate=9/1→0/10). The target fraction was concentrated under reduced pressure and dried to obtain specified in the title compound (440 mg) as a colorless transparent oil.

1H-NMR (CDCl3) δ 2,17 (4H, m), of 4.57 (2H, t, J=6.6 Hz), 6,76 (1H, d, J=3.3 Hz), 7,47 (1H, d, J=3.3 Hz), 8,72 (1H, c).

(ii) Obtaining N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-5-(4,4,4-trifloromethyl)-5H-pyrrolo[3,2-d]pyrimidine-4-amine

Specified in the title compound (171 mg) was obtained as a colourless oil interaction is similar to the method of example 38 using 4-chloro-5-(4,4,4-trifloromethyl)-5H-pyrrolo[3,2-d]pyrimidine (150 m is).

1H-NMR (CDCl3) δ 2,00-2,17 (4H, m), of 2.25 (3H, c), of 2.53 (3H, c), the 4.29 (2H, t, J=6.9 Hz), is 6.54 (1H, user. c)6,63 (1H, d, J=3.2 Hz), to 6.88 (1H, d, J=8.5 Hz), to 7.09 (1H, d, J=8.5 Hz), 7,13 (1H, DD, J=2,6, 8.5 Hz), 7,20 (1H, d, J=2.6 Hz), 7.23 percent (1H, d, J=3.2 Hz), 7,26 (1H, c), 7,32 (1H, d, J=2.6 Hz), 8,23 (1H, d, J=2.6 Hz), 8,54 (1H, c).

Example 56

Obtain N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5-[2-(2-ethoxyethoxy)ethyl]-5H-pyrrolo[3,2-d]pyrimidine-4-amine

(i) Obtaining 4-chloro-5-[2-(2-ethoxyethoxy)ethyl]-5H-pyrrolo[3,2-d]pyrimidine

To a suspension of 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (300 mg) in N,N-dimethylformamide (2.0 ml) was added cesium carbonate (728 mg) under ice cooling and the mixture was stirred, allowing to warm to room temperature over 15 minutes To the reaction mixture were added 1-bromo-2-(2-ethoxyethoxy)ethane (496 mg) and the mixture was stirred at room temperature for 20 hours the Reaction mixture was diluted with water (20 ml) and was extracted with ethyl acetate (20 ml×3). The organic layer was washed with saturated salt solution (20 ml×3) and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel (silica gel, eluent: hexane/ethyl acetate=9/1→0/10). The target fraction was concentrated under reduced pressure and dried to obtain specified in the title compound (440 mg) as a colorless transparent oil.

1H-NMR CDCl 3) δ of 1.17 (3H, t, J=7,1 Hz), 3,40-to 3.58 (6H, m), a 3.87 (2H, t, J=5,1 Hz), 4,69 (2H, t, J=5,1 Hz), 6,70 (1H, d, J=3.3 Hz), 7,63 (1H, d, J=3.3 Hz), 8,69 (1H, c).

(ii) Obtaining N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5-[2-(2-ethoxyethoxy)ethyl]-5H-pyrrolo[3,2-d]pyrimidine-4-amine

To a solution of 4-chloro-5-[2-(2-ethoxyethoxy)ethyl]-5H-pyrrolo[3,2-d]pyrimidine (150 mg) in 1-methyl-2-pyrrolidone (1.1 ml) was added 3-chloro-4-[(3-terbisil)oxy]aniline (189 mg) and the reaction mixture was stirred at 120°C for 1 h the Reaction mixture was allowed to cool to room temperature, diluted with 5% aqueous sodium hydrogen carbonate solution (25 ml) and was extracted with ethyl acetate (30 ml×3). The organic layer was washed with saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel (basic silica gel, eluent: ethyl acetate/methanol=100/0→95/5). The target fraction was concentrated under reduced pressure and dried to obtain specified in the title compound (146 mg) as a colourless oil.

1H-NMR (CDCl3) δ of 1.09 (3H, t, J=6.9 Hz), to 3.36 (2H, q, J=6.9 Hz), 3,51 (2H, t, J=4, 2 Hz), 3,71 (2H, t, J=4.5 Hz), 3,98 (2H, t, J=4.5 Hz), 4,51 (2H, t, J=4, 2 Hz), 5,24 (2H, c), 6,60 (1H, d, J=3.0 Hz), 6,91 (2H, d, J=8,8 Hz), 7,00 (2H, t, J=7.2 Hz), 7,17-7,37 (2H, m)to 7.50 (1H, DD, J=2.7, and an 8.8 Hz), to 7.68 (1H, d, J=3.0 Hz), of 8.47 (1H, c), 8,68 (1H, c).

Example 57

Getting 5-[2-(2-ethoxyethoxy)ethyl]N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

Specified in the title compound (98 mg) was obtained as a colourless oil interaction is similar to the method of example 47 using 4-chloro-5-[2-(2-ethoxyethoxy)ethyl]-5H-pyrrolo[3,2-d]pyrimidine (150 mg).

1H-NMR (DMSO-d6) δ of 0.93 (3H, t, J=7.0 Hz), 2,24 (3H, c), is 2.74 (3H, c), 3,23 (2H, q, J=7.0 Hz), 3,37 is 3.40 (2H, m), 3,56-3,59 (2H, m), 3,86 (2H, t, J=4.5 Hz), 4,89 (2H, t, J=4.5 Hz), 6,72 (1H, d, J=3.0 Hz), 7,22 (1H, d, J=8.7 Hz), 7,58-7,66 (2H, m), to $ 7.91 (1H, d, J=8.7 Hz), with 8.05 (1H, t, J=3.0 Hz), of 8.09 (1H, d, J=3.0 Hz), at 8.36 (1H, d, J=2,8 Hz), 8,73 (1H, c), 10,07 (1H, user. c).

Example 58

Getting 2-[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethanol

Specified in the title compound (241 mg) was obtained as white powder crystals by the interaction is similar to the method of example 47, using 2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethanol (250 mg).

1H-NMR (DMSO-d6) δ 2,17 (3H, c), 2,43 (3H, c), a 3.87 (2H, t, J=4.5 Hz), to 4.52 (2H, t, J=4.5 Hz), 6,27 (1H, user. c), 6,48 (1H, DD, J=1,6, 3.0 Hz), 6,97 (1H, d, J=9.6 Hz), 7,16 (1H, DDD, J=1,6, 3,0, to 8.7 Hz), 7.23 percent (1H, d, J=8,4 Hz), 7,53 (2H, user. c), 7,63 (1H, DD, J=1,6, 3.0 Hz), 8,17 (1H, d, J=3.0 Hz), of 8.28 (1H, d, J=1.6 Hz), to 9.66 (1H, user. c).

Example 59

Getting 4-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-5,6-dihydro-4H-pyrrolo[3.2.1-de]pteridine

To a suspension of 2-[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethanol (50 mg) and tribes is telefona (54 mg) in toluene (2.5 ml) was added 1,1'-[(E)-diazen-1,2-childcarer]bipiperidine (67 mg) and the mixture was stirred at room temperature for 3 hours The reaction mixture was diluted with water (15 ml) and was extracted with ethyl acetate (20 ml×3). The organic layer was washed with saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel (basic silica gel, eluent: ethyl acetate/methanol=100/0 → 90/10). The target fraction was concentrated under reduced pressure and dried to obtain specified in the title compound (36 mg) as a white powder.

1H-NMR (CDCl3) δ to 2.29 (3H, c), of 2.54 (3H, c), is 4.21 (2H, t, J=5,1 Hz)to 4.41 (2H, t, J=5,1 Hz), 6,59 (1H, d, J=2.7 Hz), 6,92 (1H, d, J=8,4 Hz), 7,11 (1H, d, J=8,4 Hz), 7,18 (1H, DD, J=2.7, and an 8.4 Hz), 7.23 percent-7,27 (2H, m), 7,38 (1H, d, J=2.7 Hz), compared to 8.26 (1H, d, J=2.7 Hz), 8,49 (1H, c).

Example 60

Obtaining 3-(5H-pyrrolo[3,2-d]pyrimidine-4-ylamino)ethylbenzoic

A mixture of 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (2,78 g), 3-aminomethylbenzoic (4,49 g) and 1-methyl-2-pyrrolidone (20 ml) was stirred at 120°C for 1.5 hours To the reaction mixture was added ethyl acetate, water and saturated aqueous solution of sodium bicarbonate. The insoluble substance was filtered and an ethyl acetate layer was separated. The aqueous layer was extracted with ethyl acetate, mixed an ethyl acetate layer was washed with saturated salt solution and dried over anhydrous magnesium sulfate. The filtered insoluble substances suspendido is whether in methanol was added ethyl acetate and a saturated solution of salt. An ethyl acetate layer was separated. An ethyl acetate layer was washed with saturated salt solution and dried over anhydrous magnesium sulfate. Mixed an ethyl acetate layer was concentrated under reduced pressure, the obtained residue was purified by chromatography on a column of silica gel (eluent: ethyl acetate) and was led from methanol-acetone-diisopropyl ether to obtain specified in the title compound (2.85 g) as pale brown powder.

1H-NMR (CDCl3) δ: of 1.39 (3H, t, J=7.2 Hz), 4,37 (2H, q, J=7.2 Hz), 6,51 (1H, d, J=3.3 Hz), 7,28-to 7.32 (1H, m), 7,42 (1H, t, J=8.0 Hz), of 7.70 (1H, d, J=7.8 Hz), of 8.09 (1H, c), 8,29 (1H, d, J=8.1 Hz), 8,49 (1H, m).

Example 61

Obtaining 3-(5H-pyrrolo[3,2-d]pyrimidine-4-ylamino)benzoic acid

A mixture of 3-(5H-pyrrolo[3,2-d]pyrimidine-4-ylamino)ethylbenzoic (3,34 g), 1H. an aqueous solution of sodium hydroxide (25 ml) and methanol (50 ml) was stirred overnight at room temperature. To the reaction mixture were added 1N. hydrochloric acid (25 ml) and evaporated under reduced pressure methanol. Precipitated precipitated crystals were separated by filtration and washed with water to obtain specified in the connection header (3,09 g) as pale brown powder.

1H-NMR (DMSO-d6) δ: 6,50 (1H, m), 7,49 (1H, t, J=7.8 Hz), 7,60 (1H, d, J=7.8 Hz), 7,69 (1H, t, J=2.7 Hz), of 8.25 (1H, d, J=7.8 Hz), 8,39 (1H, c), 8,43 (1H, c), 9,54 (1H, c), 11,24 (1H, c), 13,01 (1H, usher.).

the example 62

Obtaining N-[3-(piperidine-1-ylcarbonyl)phenyl]-5H-pyrrolo[3,2-d]pyrimidine-4-amine

A mixture of 3-(5H-pyrrolo[3,2-d]pyrimidine-4-ylamino)benzoic acid (153 mg), piperidine (0,078 ml), hydrochloride of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (173 mg) and N,N-dimethylformamide (10 ml) was stirred at room temperature for 2 hours was Added piperidine (0,078 ml) and the hydrochloride of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (173 mg) and the mixture was stirred for 1 h was Added 1-hydroxybenzotriazole (138 mg) and the mixture was stirred for 3 days. To the reaction mixture were added a saturated salt solution and the mixture was extracted with ethyl acetate. The extract was washed with saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was purified by chromatography on a column of silica gel (eluent: methanol:acetic acid ethyl ester=0:100→20:80). Added diisopropyl ether and the precipitate was separated by filtration to obtain specified in the title compound (78 mg) as pale brown powder.

1H-NMR (CDCl3) δ: of 1.56 (2H, m)of 1.73 (4H, m), 3,42 (2H, m), 3,83 (2H, m), to 6.58 (1H, d, J=2.4 Hz), make 6.90 (1H, d, J=7.5 Hz), 7.18 in-7,22 (1H, m), 7.23 percent (1H, c), 7,30 (1H, t, J=2.4 Hz), 7,88 (1H, d, J=8,3 Hz), of 8.47 (1H, c), to 8.70 (1H, c), 10,71 (1H, c).

Example 63

Obtaining N-[3-(thiomorpholine-4-ylcarbonyl)phenyl]-5H-Pirro is about[3,2-d]pyrimidine-4-amine

A mixture of 3-(5H-pyrrolo[3,2-d]pyrimidine-4-ylamino)benzoic acid (153 mg), thiomorpholine (0,091 ml), hydrochloride of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (173 mg) and N,N-dimethylformamide (10 ml) was stirred at room temperature for 2 hours was Added thiomorpholine (0,030 ml) and the hydrochloride of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (173 mg) and the mixture was stirred for 1 h was Added 1-hydroxybenzotriazole (138 mg) and the mixture was stirred for 3 days. Was added to the reaction mixture a saturated salt solution and the mixture was extracted with ethyl acetate. The extract was washed with saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was purified by chromatography on a column of silica gel (eluent: methanol:acetic acid ethyl ester=0:100→20:80). Added diisopropyl ether and the precipitate was separated by filtration. The residue was dissolved in ethyl acetate containing methanol, washed with saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure, the obtained residue was added diisopropyl ether and the precipitate was separated by filtration to obtain specified in the title compound (82 mg) as a pale brown powder.

1H-NMR (CDCl3) δ: to 2.65 (2H, m), 2,77 (2H, m), of 3.78 (2H, m), of 4.05 (2H, m), 6,59 (1H, d, J=3.0 Hz), 6,98 (1H, d, J=6.9 Hz), 7,33 (1H, d, J=7.8 Hz), 7,38(1H, d, J=3.0 Hz), 7,53 (1H, c), 7,95 (1H, usher.), 8,48 (1H, c).

Example 64

Obtain N-{3-[(4-benzylpiperidine-1-yl)carbonyl]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

A mixture of 3-(5H-pyrrolo[3,2-d]pyrimidine-4-ylamino)benzoic acid (153 mg), 4-benzylpiperidine (158 mg), hydrochloride of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (173 mg), 1-hydroxybenzotriazole (138 mg) and N,N-dimethylformamide (10 ml) was stirred at room temperature for 3 hours the Reaction mixture was concentrated under reduced pressure, was added water and the mixture was extracted with ethyl acetate containing tetrahydrofuran. The extract was washed with saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was purified by chromatography on a column of silica gel (eluent: methanol:acetic acid ethyl ester=0:100→20:80). The obtained product was dissolved in ethyl acetate containing methanol and tetrahydrofuran, washed with aqueous sodium hydrogen carbonate solution and saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was added diisopropyl ether. The precipitate was separated by filtration to obtain specified in the title compound (201 mg) as pale brown powder.

1H-NMR (CDCl3) δ: 1.10 is a 2.00 (6H, m), 2,86 (2H, d, J=6.9 Hz), of 2,75 3,05 (2H, m), 3,78-3,91 (1H, m), 4,68-4,82 (1H, m), 6,55 (1H, d, J=3.0 Hz), make 6.90 (1H, d, J=7.5 Hz), 7,10-7,33 (7H, m), 7,40 (1H, c), 7,72 (1H, d, J=8.1 Hz), to 8.45 (1H, c), 8,77 (1H, c), 10,83 (1H, c).

Example 65

Obtain N-benzyl-3-(5H-pyrrolo[3,2-d]pyrimidine-4-ylamino)benzamide

A mixture of 3-(5H-pyrrolo[3,2-d]pyrimidine-4-ylamino)benzoic acid (153 mg), benzylamine (96 mg), hydrochloride of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (173 mg), 1-hydroxybenzotriazole (138 mg) and N,N-dimethylformamide (10 ml) was stirred at room temperature for 3 days. The reaction mixture was concentrated under reduced pressure, was added water and the mixture was extracted with ethyl acetate containing tetrahydrofuran. The extract was washed with saturated aqueous sodium hydrogen carbonate solution and saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was purified by chromatography on a column of silica gel (eluent: methanol:acetic acid ethyl ester=0:100→50:50). Added ethyl acetate and diethyl ether and the precipitate was separated by filtration to obtain specified in the title compound (128 mg) as colorless powder.

1H-NMR (DMSO-d6) δ: 4,50 (2H, d, J=6.0 Hz), of 6.49 (1H, m), 7,21-7,38 (5H, m), 7,46 (1H, t, J=8.0 Hz), 7,55 (1H, d, J=8.1 Hz), to 7.68 (1H, t, J=3.0 Hz), 8,19 (1H, c), compared to 8.26 (1H, d, J=8.0 Hz), of 8.37 (1H, c), 9,06 (1H, t, J=6,0 Hz), 9,41 (1H, c), 11,13 (1H, c).

Example 66

Obtaining [2-(benzyloxy)-5-(5H-pyrrolo[3,2-d]pyrimidine-4-ylamino)phenyl]methanol

A mixture of 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (307 mg), [5-amino-2-(benzyloxy)phenyl]methanol (459 mg) and N,N-dimethylformamide (10 ml) was stirred at 80°C for 4 h the Reaction mixture was concentrated under reduced pressure, was added an aqueous solution of sodium bicarbonate and the mixture was extracted with ethyl acetate containing tetrahydrofuran. The extract was washed with saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was purified by chromatography on a column of silica gel (eluent: methanol:acetic acid ethyl ester=0:100→30:70). Added ethanol and ethyl acetate and the precipitate was separated by filtration to obtain specified in the title compound (279 mg) as a brown powder.

1H-NMR (DMSO-d6) δ: 4,60 (2H, d, J=5.5 Hz), 5,12 (2H, c)to 5.17 (1H, t, J=5.5 Hz), 6,45 (1H, m), 7,03 (1H, d, J=8,8 Hz), 7,29-7,51 (5H, m), a 7.62 (1H, t, J=2,9 Hz), the 7.65 (1H, d, J=2.7 Hz), to 7.93 (1H, DD, J=8,8, 2.7 Hz), 8,29 (1H, c), the remaining 9.08 (1H, c)11,05 (1H, c).

Example 67

Obtaining N-[4-(benzyloxy)-3-methoxyphenyl]-5H-pyrrolo[3,2-d]pyrimidine-4-amine

A mixture of 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (200 mg), 4-(benzyloxy)-3-methoxyaniline (298 mg) and 1-methyl-2-pyrrolidone (5 ml) was stirred at 80°C for 4 h Methanol and activated carbon was added to the reaction mixture and the MCA is ü mixed. Activated charcoal was filtered, was added an aqueous solution of sodium bicarbonate and the mixture was extracted with ethyl acetate. The extract was washed with saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was purified by chromatography on a column of silica gel (eluent: methanol:ethyl acetate=10:80→20:80) and recrystallized from methanol-ethyl acetate to obtain specified in the title compound (269 mg) as a pale grey powder.

1H-NMR (DMSO-d6) δ: 3,82 (3H, c), is 5.06 (2H, c), of 6.45 (1H, m), 7,03 (1H, d, J=8,9 Hz), 7,30-7,49 (6H, m), 7,51 (1H, d, J=2.5 Hz), 7,63 (1H, t, J=2,9 Hz), 8,30 (1H, c), 9,07 (1H, c), 11,06 (1H, c).

Example 68

Obtaining N-[4-(benzyloxy)-3-chlorophenyl]-5H-pyrrolo[3,2-d]pyrimidine-4-amine

A mixture of 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (200 mg), 4-(benzyloxy)-3-Chloroaniline (365 mg) and 1-methyl-2-pyrrolidone (3 ml) was stirred at 80°C for 4 h Methanol and activated carbon was added to the reaction mixture and the mixture was stirred. Activated charcoal was filtered, was added an aqueous solution of sodium bicarbonate and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was purified by chromatography on to the column with silica gel (eluent: methanol:ethyl acetate=0:100→15:75) and recrystallized from a mixture of ethanol-ethyl acetate to obtain specified in the title compound (226 mg) as a pale brown powder.

1H-NMR (CDCl3) δ: 5,15 (2H, c), 6,56 (1H, c), 6,98 (1H, d, J=8,9 Hz), 7,28-the 7.43 (4H, m), of 7.48 (2H, d, J=7.5 Hz), 7,69 (1H, d, J=8,9 Hz), 7,80 (1H, d, J=2,6 Hz)and 8.50 (1H, c), 8,63 (1H, c), 10,56 (1H, c).

Example 69

Getting 2-phenoxy-5-(5H-pyrrolo[3,2-d]pyrimidine-4-ylamino)ethylbenzoic

A mixture of ethyl-4-chloro-5H-pyrrolo[3,2-d]pyrimidine (461 mg), 5-amino-2-phenoxybenzoate (926 mg) and 1-methyl-2-pyrrolidone (5 ml) was stirred at 80°C for 2 hours, the Ethanol, water and activated charcoal was added to the reaction mixture and the mixture was stirred. The activated carbon was filtered and the solvent evaporated under reduced pressure. To the residue was added an aqueous solution of sodium bicarbonate and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was purified by chromatography on a column of silica gel (eluent: methanol:ethyl acetate=0:100→20:80) and recrystallized from a mixture of ethanol-ethyl acetate to obtain specified in the title compound (572 mg) as colorless powder.

1H-NMR (CDCl3) δ: of 1.12 (3H, t, J=7,1 Hz), 4,19 (2H, q, J=7,1 Hz), to 6.57 (1H, d, J=3.0 Hz), at 6.84 (2H, d, J=7,7 Hz), to 6.95 (1H, d, J=8,9 Hz), 7,00 (1H, t, J=7,3 Hz), 7,19-7,29 (2H, m), 7,34 (1H, d, J=3.0 Hz), 7,80 (1H, DD, J=8,9, 2,8 Hz), 8,00 (1H, d, J=2,8 Hz), 8,67 (1H, c), 8,87 (1H, c), 10,89 (1H, c).

Example 70

Getting 2-phenoxy-5-(5H-pyrrolo[3,2-d]pyrimidine-4-ylamino)benzoic acid

A mixture of 2-phenoxy-5-(5H-pyrrolo[3,2-d]pyrimidine-4-ylamino)ethylbenzoic (899 mg), 1H. an aqueous solution of sodium hydroxide (5 ml) and methanol (15 ml) was stirred at 60°C for 1.5 hours To the reaction mixture were added 1N. hydrochloric acid (5 ml) and evaporated under reduced pressure methanol. Precipitated precipitated crystals were separated by filtration and washed with water and acetone to obtain specified in the header of the compound (768 mg) as pale brown powder.

1H-NMR (DMSO-d6) δ: 6,50 (1H, m), 6.89 in (2H, d, J=7,7 Hz),? 7.04 baby mortality (1H, t, J=7,3 Hz), 7,12 (1H, d, J=8,9 Hz), 7,33 (2H, t, J=8.0 Hz), 7,69 (1H, t, J=2,9 Hz), 8,16 (1H, DD, J=8,9, 2,9 Hz), 8,31 (1H, d, J=2,9 Hz), of 8.37 (1H, c)9,46 (1H, c), of 11.11 (1H, c), to 12.95 (1H, usher.).

Example 71

Obtaining [2-phenoxy-5-(5H-pyrrolo[3,2-d]pyrimidine-4-ylamino)phenyl]methanol

To a solution of 2-phenoxy-5-(5H-pyrrolo[3,2-d]pyrimidine-4-ylamino)benzoic acid (173 mg) in N,N-dimethylformamide (5 ml) was added 1,1'-carbonyldiimidazole (97 mg) and the mixture was stirred at room temperature for 1 h sodium Borohydride (38 mg) was added to the reaction mixture at room temperature and methanol (1 ml) was added dropwise. After stirring overnight at room temperature, the reaction mixture was added water and the mixture was extracted with ethyl acetate. Extract amywali water and saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was purified by chromatography on a column of silica gel (eluent: methanol:ethyl acetate=0:100→20:80) and was led from methanol-ethyl acetate to obtain specified in the title compound (44 mg) as colorless powder.

1H-NMR (DMSO-d6) δ: 4,50 (2H, d, J=5,1 Hz), 5,28 (1H, t, J=5,1 Hz), 6.48 in (1H, m), of 6.90 (2H, d, J=7,7 Hz), of 6.96 (1H, d, J=8.7 Hz), 7,06 (1H, t, J=7,3 Hz), 7,30-7,40 (2H, m), 7,66 (1H, t, J=2,9 Hz), the 7.85 (1H, d, J=2,7 Hz), of 8.04 (1H, DD, J=8,7, 2.7 Hz), a 8.34 (1H, c), 9.28 are (1H, c), of 11.11 (1H, c).

Example 72

Obtain 6-(2-furyl)-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

(i) Obtain 2-cyano-1-(2-furyl)vinyl 4-methylbenzenesulfonate

To a mixture of 3-(2-furyl)-3-oxopropanenitrile (5.29 g), p-toluensulfonate (9.00 g) and dichloromethane (60 ml) was added drop wise addition of triethylamine (of 5.99 g) under cooling with ice. After stirring under ice cooling for 1.5 h the mixture was diluted with dichloromethane (100 ml). The mixture was washed with water (150 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (eluent: hexane:acetate=9:1→3:1) to obtain specified in the connection header (10,48 g) in a mixture of (E)-form and (Z)-shape (3:1).

1H-NMR (CDCl3) δ 2,47 (3/4H, c), 2,49 (9/4H, c), 5,27 (1/4H, c), 5,63 (3/4H, c), 6,47 (1/4H, m) 6,53 (3/4H, m)6,86 (1/4H, d, J=3.6 Hz), 6,95 (3/4H, d, J=3.6 Hz), 7,38 (1/2H, d, J=7.8 Hz), 7,42 (3/2H, d, J=7.8 Hz), 7,51 (3/4H, m), 7,55 (1/4H, m), 7,83 (1/2H, d, J=7.8 Hz), 7,97 (3/2H, d, J=7,8 Hz).

(ii) Obtaining 3-amino-5-(2-furyl)-1H-pyrrol-2-ethylcarboxylate

To a solution of 2-cyano-1-(2-furyl)vinyl 4-methylbenzenesulfonate (10,48 g) and hydrochloride diethylaminoacetate (to 7.67 g) in a mixed solvent of ethanol (120 ml)-tetrahydrofuran (64 ml) was added dropwise a solution of (36,9 ml) 20% ethoxide sodium in ethanol under cooling with ice. After stirring at room temperature for 12 h, the reaction mixture was poured into ice water (350 ml) and the mixture is brought to pH 7 by adding 1N. hydrochloric acid. The organic solvent evaporated under reduced pressure and the residue was extracted with ethyl acetate (150 ml×3). The organic layers were combined, washed with saturated salt solution (100 ml) and dried over anhydrous magnesium sulfate. After concentration under reduced pressure the residue was purified by chromatography on a column of silica gel (eluent: hexane:acetate=3:1→1:1) and the obtained solid substance was recrystallized from a mixture of ethyl acetate-hexane to obtain specified in the title compound (2.66 g).

1H-NMR (CDCl3) δ of 1.37 (3H, t, J=7.0 Hz), 4,34 (2H, q, J=7.0 Hz), 4,37 (2H, user. c)to 5.93 (1H, d, J=2.7 Hz), 6,45 (1H, DD, J=3,6, 1.8 Hz), of 6.49 (1H, d, J=3.6 Hz), 7,41 (1H, d, J=1,8 Hz), 8,35 (1H, user. c).

(iii) Obtain 6-(2-furyl)-4,5-dihydro-3H-pyrrolo[3,2-d-4-it

To a solution of 3-amino-5-(2-furyl)-1H-pyrrol-2-ethylcarboxylate (2.58 g) in ethanol (35 ml) was added formamidine (1,83 g) and the mixture is boiled under reflux for 18 hours After cooling to room temperature, precipitated precipitated solid substance was separated by filtration, washed with ethanol and dried under reduced pressure at 60°C with obtaining specified in the connection header (of 2.26 g).

1H-NMR (DMSO-d6) δ to 6.58 (1H, d, J=2.1 Hz), is 6.61 (1H, DD, J=3,5, and 2.1 Hz), was 7.08 (1H, m), 7,76 (1H, m), 7,80 (1H, d, J=3.5 Hz), 11,91 (1H, user. c)12,50 (1H, user. c).

(iv) Obtain 4-chloro-6-(2-furyl)-5H-pyrrolo[3,2-d]pyrimidine

A mixture of 6-(2-furyl)-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidine-4-it (2.20 g) and phosphorylchloride (10.7 g) was stirred at 100°C for 20 min, was added dioxane (30 ml) and the mixture was stirred at 100°C for 3 hours After concentration under reduced pressure, saturated aqueous sodium hydrogen carbonate solution was added to the residue and the mixture was extracted with a mixture of ethyl acetate-acetone (155 ml×4). The organic layers were combined, washed with saturated salt solution (100 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was washed with a mixture of ethyl acetate-diethyl ether and dried under reduced pressure at 60°C with obtaining specified in the connection header (2,19 g).

1H-NMR (DMSO-d6) δ 6,74 (1H, DD, J=3,6, and 2.1 Hz), to 6.95 (1H, d, J=1,8 Hz), 7,37 (1, DD, J=3,6, 0.6 Hz), 7,95 (1H, DD, J=2,1, 0.6 Hz), at 8.60 (1H, c), 12,71 (1H, user. c).

(v) Obtain 6-(2-furyl)-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

A mixture of 4-chloro-6-(2-furyl)-5H-pyrrolo[3,2-d]pyrimidine (110 mg), 3-methyl-4-[(6-methylpyridin-3-yl)oxy]aniline (161 mg) and 1-methyl-2-pyrrolidinone (2.5 ml) was stirred at 140°C for 2 h, poured into water (10 ml) and the mixture is brought to pH 8 with saturated aqueous solution of sodium bicarbonate. The mixture was extracted with ethyl acetate (25 ml×2), the organic layers were combined and dried over anhydrous magnesium sulfate. After concentration under reduced pressure the residue was subjected to chromatography on a column of silica gel (eluent: hexane:ethyl acetate=1:1→0:1). The target fraction was concentrated under reduced pressure. Was added to the residue, the mixture of chloroform-diisopropyl ether, the solid was separated by filtration and dried under reduced pressure at 60°C with obtaining specified in the title compound (114 mg).

1H-NMR (DMSO-d6) δ of 2.21 (3H, c), 2,48 (3H, c), 6,72 (1H, DD, J=3.3, which is 1.8 Hz), 6,78 (1H, d, J=1,8 Hz), 6,98 (1H, d, J=8,4 Hz), 7,02 (1H, d, J=3.6 Hz), 7,17 (1H, DD, J=8,4, 2.7 Hz), 7,22 (1H, d, J=8,4 Hz), 7,74 (1H, DD, J=of 8.4 and 2.7 Hz), 7,80 (1H, d, J=2.1 Hz), 7,92 (1H, DD, J=1,8, 0.9 Hz), 8,16 (1H, DD, J=2.7, and 0.9 Hz), with 8.33 (1H, c), 9,17 (1H, user. c)11,67 (1H, user. c).

Example 73

Obtain N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-6-(2-furyl)-5H-pyrrolo[3,2-d]pyrimidine-4-AMI is and

A mixture of 4-chloro-6-(2-furyl)-5H-pyrrolo[3,2-d]pyrimidine (110 mg), 3-chloro-4-[(3-terbisil)oxy]aniline (189 mg) and 1-methyl-2-pyrrolidinone (2.5 ml) was stirred at 140°C for 2 h, poured into water (10 ml) and the mixture is brought to pH 8 with saturated aqueous solution of sodium bicarbonate. The mixture was extracted with ethyl acetate (30 ml×2). The organic layers were combined and dried over anhydrous magnesium sulfate. After concentration under reduced pressure the residue was subjected to chromatography on a column of silica gel (eluent: hexane:ethyl acetate=4:1→1:1). The target fraction was concentrated under reduced pressure. To the residue was added a mixture of chloroform-diisopropyl ether, the solid was separated by filtration and dried under reduced pressure at 60°C with obtaining specified in the title compound (122 mg).

1H-NMR (DMSO-d6) δ 5,23 (2H, c), of 6.71 (1H, DD, J=3.3, which is 2.1 Hz), 6,78 (1H, d, J=2.1 Hz), 7,02 (1H, d, J=3.3 Hz), 7,18 (1H, m), 7,25 (1H, d, J=9.0 Hz), 7,28-7,33 (2H, m), 7,46 (1H, m), EUR 7.57 (1H, DD, J=9,0, 3.0 Hz), 7,92 (1H, d, J=1,8 Hz), 8,18 (1H, d, J=2.4 Hz), with 8.33 (1H, c), 9,18 (1H, user. c), to 11.61 (1H, user. c).

Example 74

Obtaining N-[3-chloro-4-(pyridine-2-ylethoxy)phenyl]-6-(2-furyl)-5H-pyrrolo[3,2-d]pyrimidine-4-amine

A mixture of 4-chloro-6-(2-furyl)-5H-pyrrolo[3,2-d]pyrimidine (80 mg), 3-chloro-4-(pyridine-2-ylethoxy)aniline (94 mg) and 1-methyl-2-pyrrolidinone (2.5 ml) was stirred at 140°C for 2 h, poured into water (10 ml) and the mixture up to the-Odile to pH 8 with saturated aqueous solution of sodium bicarbonate. The mixture was extracted with ethyl acetate (30 ml×2). The organic layers were combined and dried over anhydrous magnesium sulfate. After concentration under reduced pressure the residue was subjected to chromatography on a column of silica gel (eluent: hexane:ethyl acetate=1:1→0:1). The target fraction was concentrated under reduced pressure. To the residue was added a mixture of chloroform-diisopropyl ether, the solid was separated by filtration and dried under reduced pressure at 60°C with obtaining specified in the title compound (71 mg).

1H-NMR (DMSO-d6) δ 5,27 (2H, c), 6,72 (1H, m), is 6.78 (1H, d, J=1.2 Hz), 7,02 (1H, d, J=3.3 Hz), 7,26 (1H, d, J=9.0 Hz), was 7.36 (1H, m), 7,53-to 7.59 (2H, m), 7,81 (1H, d, J=8.1 Hz), to $ 7.91 (1H, c), 8,21 (1H, d, J=2.4 Hz), 8.34 per (1H, c), 8,59 (1H, d, J=5,1 Hz), 9,19 (1H, user. c), are 11.62 (1H, user. c).

Example 75

Getting hydrochloride 4-[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]benzoic acid

(i) Obtaining 4-(2-cyano-1-{[(4-were)sulfonyl]oxy}vinyl)methylbenzoate

To a mixture of 4-(cyanoacetyl)methylbenzoate (10,29 g), p-toluensulfonate (11,58 g) and dichloromethane (110 ml) was added drop wise addition of triethylamine (of 7.68 g) under cooling with ice. After stirring under ice cooling for 2.5 h the mixture was diluted with dichloromethane (100 ml), washed with water (150 ml), dried over anhydrous magnesium sulfate and concentrated under reduced on the no. The residue was purified by chromatography on a column of silica gel (eluent: hexane:acetate=9:1→1:1) to obtain specified in the connection header (17,60 g) in a mixture of (E)-form and (Z)-forms (6:5).

1H-NMR (CDCl3) δ 2,44 (18/11H, c), 2,47 (15/11H, c)3,94 (18/11H, c), 3,95 (15/11H, c), 5,66 (6/11H, c)5,68 (5/11H, c), 7,33 (12/11H, d, J=7.8 Hz), 7,38 (10/11H, d, J=7.8 Hz), 7,62-8,09 (6H, m).

(ii) Obtaining 3-amino-5-[4-(etoxycarbonyl)phenyl]-1H-pyrrol-2-ethylcarboxylate

To a suspension of 4-(2-cyano-1-{[(4-were)sulfonyl]oxy}vinyl)methylbenzoate (17.5 g) and hydrochloride diethylaminoacetate (10,36 g) in a mixed solvent of ethanol (165 ml)-tetrahydrofuran (80 ml) was added dropwise a solution (50 ml), 20% ethoxide sodium in ethanol under cooling with ice. After stirring under ice cooling for 1 h the mixture was stirred at room temperature for 21 hours, the Reaction mixture was poured into ice water (400 ml) and brought to pH 7 by adding 1N. hydrochloric acid. The organic solvent evaporated under reduced pressure and the residue was extracted with ethyl acetate (250 ml×3). The organic layers were combined, washed with saturated salt solution (150 ml) and dried over anhydrous magnesium sulfate. After concentration under reduced pressure the residue was purified by chromatography on a column of silica gel (eluent: hexane:ethyl acetate=2:1→1:1) and the obtained solid substance was recrystallized from a mixture is ethyl acetate to obtain specified in the connection header (4,76 g).

1H-NMR (CDCl3) δ 1,36 was 1.43 (6H, m), or 4.31 was 4.42 (6H, m), 6,11 (1H, d, J=3.0 Hz), 7,55 (2H, d, J=8,4 Hz), of 8.04 (2H, d, J=8,4 Hz), 8,40 (1H, user. c).

(iii) Obtaining 4-(4-oxo-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidine-6-yl)ethylbenzoic

A mixture of 3-amino-5-[4-(etoxycarbonyl)phenyl]-1H-pyrrol-2-ethylcarboxylate (3,36 g), formamidine (1,74 g) and ethanol (60 ml) was boiled under reflux for 15 hours After cooling to room temperature, precipitated precipitated solid substance was separated by filtration, washed with ethanol and dried under reduced pressure at 60°C with obtaining specified in the connection header (2,97 g).

1H-NMR (DMSO-d6) δ of 1.34 (3H, t, J=7,1 Hz)to 4.33 (2H, q, J=7,1 Hz),? 7.04 baby mortality (1H, c), to 7.84 (1H, d, J=2.7 Hz), 8,00 (2H, d, J=8.1 Hz), 8,11 (2H, d, J=8.1 Hz), of $ 11.97 (1H, user. c), 12,64 (1H, user. c).

(iv) obtaining the hydrochloride of 4-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-6-yl)ethylbenzoic

A mixture of 4-(4-oxo-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidine-6-yl)ethylbenzoic (2,97 g) and phosphorylchloride (16,45 g) was stirred at 110°C for 1 h, was added dioxane (10 ml) and the mixture is boiled under reflux for 4 hours After concentration under reduced pressure, to the residue was added ethanol (30 ml) and after stirring at room temperature for 30 min precipitated precipitated solid substance was separated by filtration. The solid is washed with ethanol and dried under reduced pressure at 60°C with getting ukazannoj is in the connection header (3,34 g).

1H-NMR (DMSO-d6) δ of 1.36 (3H, d, J=7,1 Hz), 4,36 (2H, q, J=7,1 Hz), 7,40 (1H, c), of 8.09 (2H, d, J=8.7 Hz), compared to 8.26 (2H, d, J=8.7 Hz), 8,67 (1H, c), 12,77 (1H, user. c).

(v) Obtaining hydrochloride 4-[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]benzoic acid

A mixture of the hydrochloride of 4-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-6-yl)ethylbenzoic (1,297 g), 3-methyl-4-[(6-methylpyridin-3-yl)oxy]aniline (1,00 g), diisopropylethylamine (0,834 g) and 1-methyl-2-pyrrolidinone (12.5 ml) was stirred at 140°C for 3 h, poured into a mixture of water (100 ml)-ethyl acetate (150 ml) and precipitated in the sediment solid was separated by filtration. The solid is washed with ethyl acetate and dried under reduced pressure at 60°C. the Obtained solid is suspended in methanol (40 ml) was added 1N. an aqueous solution of sodium hydroxide (20 ml). After stirring at room temperature for 12 h, the solvent evaporated under reduced pressure and the residue was brought to pH 2 by adding 1N. hydrochloric acid. Precipitated precipitated solid substance was separated by filtration, washed with water and dried under reduced pressure at 60°C with obtaining specified in the title compound (1.08 g).

1H-NMR (DMSO-d6) δ of 2.21 (3H, c), is 2.44 (3H, c), 6,98 (1H, d, J=9.0 Hz), to 7.15 (1H, c), 7,17-of 7.25 (2H, m), 7,76 (1H, d, J=8.7 Hz), the 7.85 (1H, c), 8,01-8,17 (5H, m), 8,48 (1H, c), 9,99 (1H, user. c), 12,47 (1H, user. c).

Example 76

Getting hydrochloride 4-[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]benzoic acid

A mixture of the hydrochloride of 4-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-6-yl)ethylbenzoic (517 mg), 3-chloro-4-[(3-terbisil)oxy]aniline (462 mg) and 1-methyl-2-pyrrolidinone (8 ml) was stirred at 140°C for 5 h, poured into water (40 ml) and brought to pH 8 with saturated aqueous solution of sodium bicarbonate. Precipitated precipitated solid substance was separated by filtration, washed with water and suspended in methanol (15 ml). After stirring at room temperature for 30 min, the solid was separated by filtration and dried under reduced pressure at 60°C. the Obtained solid is suspended in ethanol (10 ml) was added 1N. an aqueous solution of sodium hydroxide (1.5 ml). After stirring at room temperature for 6.5 h and at 60°C for 3.5 h the mixture was cooled to room temperature. Added 1N. hydrochloric acid (155 ml) and precipitated precipitated solid substance was separated by filtration, washed with water and dried under reduced pressure at 60°C with obtaining specified in the title compound (498 mg).

1H-NMR (DMSO-d6) ∆ 5,24 (2H, c), 7,12-to 7.35 (5H, m), of 7.48 (1H, m), of 7.70 (1H, d, J=8.7 Hz), 8,01-to 8.12 (4H, m), of 8.27 (1H, c), of 8.37 (1H, c), 9,65 (1H, user. c), 12,15 (1H, user. c).

Example 77

Obtain 6-(2-furyl)--methyl-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

(i) Obtaining 4-chloro-6-(2-furyl)-5-methyl-5H-pyrrolo[3,2-d]pyrimidine

To a solution of 4-chloro-6-(2-furyl)-5H-pyrrolo[3,2-d]pyrimidine (220 mg) in N,N-dimethylformamide (2.5 ml) was added potassium carbonate (139 mg) and methyliodide (0.25 ml) and the mixture was stirred at room temperature for 8 hours the Mixture was poured into water (30 ml) and was extracted with ethyl acetate (30 ml×3). The organic layers were combined and dried over anhydrous magnesium sulfate. After concentration under reduced pressure the residue was subjected to chromatography on a column of silica gel (eluent: hexane:ethyl acetate=4:1→0:1) to obtain the specified title compound (94 mg).

1H-NMR (CDCl3) δ 4,29 (3H, c), 6,62 (1H, DD, J=3,6, 1.8 Hz), 6,86 (1H, d, J=3.6 Hz), 6,94 (1H, c), to 7.67 (1H, d, J=1,8 Hz), 8,68 (1H, c).

(ii) Obtain 6-(2-furyl)-5-methyl-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

A mixture of 4-chloro-6-(2-furyl)-5-methyl-5H-pyrrolo[3,2-d]pyrimidine (92 mg), 3-methyl-4-[(6-methylpyridin-3-yl)oxy]aniline (102 mg) and 1-methyl-2-pyrrolidinone (2.5 ml) was stirred at 140°C for 3.5 hours, poured into water (10 ml) and the mixture is brought to pH 8 with saturated aqueous solution of sodium bicarbonate. The mixture was extracted with ethyl acetate (25 ml×2), the organic layers were combined and dried over anhydrous magnesium sulfate. After concentration under reduced pressure the residue was subjected to chromatography on a column of silica gel (eluent: hexanitrate=1:1→0:1). The target fraction was concentrated under reduced pressure. To the residue was added diethyl ether, the solid was separated by filtration and dried under reduced pressure at 60°C with obtaining specified in the title compound (105 mg).

1H-NMR (DMSO-d6) δ 2,17 (3H, c), 2,43 (3H, c), of 4.12 (3H, c), 6,74 (1H, DD, J=3,6, 1.2 Hz), 6,76 (1H, c), 6,93 (1H, d, J=8.7 Hz), 7,05 (1H, d, J=3.6 Hz), 7,17 (1H, DD, J=8,7, 2.4 Hz), 7.23 percent (1H, d, J=8.7 Hz), 7,46 (1H, DD, J=8,7, 3.0 Hz), 7,52 (1H, d, J=2.4 Hz), 7,94 (1H, d, J=1.2 Hz), 8,16 (1H, d, J=3.0 Hz), of 8.27 (1H, c), 8,71 (1H, user. c).

Example 78

Getting 5-(2-ethoxyethyl)-6-(2-furyl)-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

(i) Obtaining 4-chloro-5-(2-ethoxyethyl)-6-(2-furyl)-5H-pyrrolo[3,2-d]pyrimidine

To a solution of 4-chloro-6-(2-furyl)-5H-pyrrolo[3,2-d]pyrimidine (220 mg) in N,N-dimethylformamide (1.2 ml) was added cesium carbonate (489 mg) under ice cooling and the mixture was stirred under ice cooling for 15 minutes was Added 2-bromatology ether (0,169 ml) and the mixture was stirred at room temperature for 2 days. Added cesium carbonate (326 mg) and 2-bromatology ether (0,113 ml) and the mixture was stirred at room temperature for 1 day. The reaction mixture was poured into water (30 ml) and was extracted with ethyl acetate (60 ml). The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. OST the current was subjected to chromatography on a column of silica gel (eluent: hexane:ethyl acetate=4:1→1:4) to obtain the specified title compound (76 mg).

1H-NMR (CDCl3) δ of 1.09 (3H, t, J=6.9 Hz), 3,42 (2H, q, J=6.9 Hz), 3,82 (2H, t, J=6.3 Hz), to 4.92 (2H, t, J=6.3 Hz), 6,60 (1H, DD, J=3,6, and 2.1 Hz), 6,94 (1H, c), 6,98 (1H, d, J=3.6 Hz), to 7.64 (1H, d, J=2.1 Hz), 8,68 (1H, c).

(ii) Obtaining 5-(2-ethoxyethyl)-6-(2-furyl)-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

A mixture of 4-chloro-5-(2-ethoxyethyl)-6-(2-furyl)-5H-pyrrolo[3,2-d]pyrimidine (76 mg), 3-methyl-4-[(6-methylpyridin-3-yl)oxy]aniline (67 mg) and 1-methyl-2-pyrrolidinone (1.5 ml) was stirred at 140°C for 2 h, poured into water (8 ml) and the mixture is brought to pH 8 with saturated aqueous solution of sodium bicarbonate. The mixture was extracted with ethyl acetate (20 ml×2) and the organic layers were combined and dried over anhydrous magnesium sulfate. After concentration under reduced pressure the residue was subjected to chromatography on a column of silica gel (eluent: hexane:ethyl acetate=1:1→0:1). The target fraction was concentrated under reduced pressure. To the residue was added a mixture of diisopropyl ether-hexane, the solid was separated by filtration and dried under reduced pressure at 60°C with obtaining specified in the title compound (78 mg).

1H-NMR (DMSO-d6) δ a 1.08 (3H, t, J=6.9 Hz), to 2.18 (3H, c), 2,43 (3H, c), 3,52 (2H, q, J=6.9 Hz), of 3.95 (2H, t, J=4.4 Hz), and 4.68 (2H, ushort, J=4.4 Hz), was 6.73 (1H, DD, J=3,6, 1.8 Hz), at 6.84 (1H, c), of 6.96 (1H, d, J=8.1 Hz), 7,01 (1H, d, J=3.6 Hz), 7,16 (1H, DD, J=8,4, 2.7 Hz), 7,22 (1H, d, J=8,4 Hz), 7,50-of 7.55 (2H, m), to 7.93 (1H, d, J=1,8 Hz), 8,15 (1H, d, J=2.7 Hz), 8,31 (1H, c)to 9.15 (1H, users).

Example 79

Obtain {4-[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]phenyl}methanol

To a suspension of 4-[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]benzoic acid (122 mg) in tetrahydrofuran (10 ml) was added triethylamine (30,5 mg), after stirring at room temperature for 10 min was added 1,1'-carbonyldiimidazole (49 mg) and the mixture was stirred at room temperature for 13 hours Under ice cooling was added sodium borohydride (28 mg) and then further added methanol (2.5 ml). After stirring under ice cooling for 2 h, was added water (1.5 ml) and tetrahydrofuran and methanol evaporated under reduced pressure. Was added water (20 ml) the mixture was extracted with a mixture of ethyl acetate (30 ml)-tetrahydrofuran (15 ml). The organic layer was separated and the aqueous layer was extracted with a mixture of ethyl acetate (15 ml)-tetrahydrofuran (5 ml). The organic layers were combined and dried over anhydrous magnesium sulfate. After concentration under reduced pressure the residue was subjected to chromatography on a column of silica gel (eluent: ethyl acetate:methanol=99:1→9:1). The target fraction was concentrated under reduced pressure. The residue was recrystallized from methanol-ethyl acetate to obtain specified in the connection header (MH).

1H-NMR (DMSO-d6) δ of 2.21 (3H, c), 2,43 (3H, c), of 4.57 (2H, d, J=4,8 Hz), 5,32 (1H, ushort, J=4,8 Hz), of 6.96 (1H, c), of 6.99 (1H, d, J=8,4 Hz), 7,18 (1H, DD, J=8,7, 2.7 Hz), 7.23 percent (1H, d, J=8.7 Hz), to 7.50 (2H, d, J=7.8 Hz), 7,74 (1H, DD, J=8,4, 2.7 Hz), 7,81-a 7.85 (3H, m), 8,16 (1H, d, J=2.7 Hz), a 8.34 (1H, c), which is 9.09 (1H, user. c), to 11.56 (1H, user. c).

Example 80

Obtain N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-6-[4-({[2-(methylsulphonyl)ethyl]amino}methyl)phenyl]-5H-pyrrolo[3,2-d]pyrimidine-4-amine

A mixture of {4-[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]phenyl}methanol (96 mg), manganese dioxide (1.0 g) and N,N-dimethylformamide (5 ml) was stirred at room temperature for 12 hours After filtration through celite the filtrate was concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel (eluent: ethyl acetate:methanol=100:0→9:1). A mixture of the obtained solid, hydrochloride methylsulfonylamino (27.5 mg), N,N-dimethylformamide (2 ml) and acetic acid (0,02 ml) was stirred at room temperature for 1 h and added triacetoxyborohydride sodium (36,6 mg). After stirring at room temperature for 4.5 h, saturated aqueous sodium hydrogen carbonate solution (10 ml) was added and the mixture was extracted with ethyl acetate (25 ml×2). The organic layers were combined, dried over anhydrous magnesium sulfate and concentrated at below the nom pressure. The residue was subjected to chromatography on a column of silica gel (ethyl acetate:methanol=10:0→9:1). The target fraction was concentrated under reduced pressure. To the residue was added a mixture of chloroform-diisopropyl ether, the solid was separated by filtration and dried under reduced pressure at 60°C with obtaining specified in the title compound (28 mg).

1H-NMR (DMSO-d6) δ of 2.21 (3H, c), is 2.44 (3H, c)to 2.94 (2H, t, J=6,6 Hz)of 3.00 (3H, c), 3,29 (2H, t, J=6.6 Hz), of 3.78 (2H, c), 6,97 (1H, c), of 7.00 (1H, d, J=8.7 Hz), 7,19 (1H, DD, J=8,4, 2.7 Hz), 7,24 (1H, d, J=8,4 Hz), 7,51 (2H, d, J=8,4 Hz), to 7.77 (1H, DD, J=8,7, 2.4 Hz), 7,83-7,87 (3H, m), 8,18 (1H, d, J=2.4 Hz), a 8.34 (1H, c), 9,23 (1H, user. c)11,73 (1H, user. c).

Example 81

Getting dihydrochloride 6-(aminomethyl)-N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

(i) produce N4-{3-chloro-4-[(3-terbisil)oxy]phenyl}-6-iodopyrimidine-4,5-diamine

A solution of 5-amino-4,6-diatpillen (a 3.83 g) and 3-chloro-4-[(3-terbisil)oxy]aniline (2,78 g) in 1-methyl-2-pyrrolidone (30 ml) was stirred at 70°C for 14 hours was Added to the reaction system of water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated salt solution and dried over magnesium sulfate. After concentration under reduced pressure the residue was separated and purified column chromatography (eluent: ethyl acetate:hexane=1:4→2:3→1:1) obtaining specified in the header is soedineniya (4,21 g) as brown powder crystals.

1H-NMR (CDCl3) δ: 3,47 (2H, user. c)to 5.13 (2H, c), of 6.73 (1H, user. c), 6,92 (1H, d, J=9.0 Hz), of 6.96? 7.04 baby mortality (1H, m), 7,15-of 7.25 (2H, m), 7,31-7,38 (2H, m), of 7.64 (1H, d, J=2.7 Hz), of 8.04 (1H, c).

(ii) Obtaining tert-butyl-3-[5-amino-6-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)pyrimidine-4-yl]prop-2-vinylcarbazole

To a solution of N4-{3-chloro-4-[(3-terbisil)oxy]phenyl}-6-iodopyrimidine-4,5-diamine (0.84 g) and tert-boolprop-2-vinylcarbazole (0.36 g) in a mixture of acetonitrile-triethylamine (20 ml 15 ml) was added dichloride bis(triphenylphosphine)palladium(II) (62.5 mg) and copper iodide(I) (a 20.3 mg) at room temperature and the mixture was stirred at room temperature in an argon atmosphere for 6 hours After concentration under reduced pressure, the residue was separated and purified column chromatography (eluent: ethyl acetate:hexane=1:1→ethyl acetate) to obtain specified in the connection header (the 766.5 mg) as a brown solid.

1H-NMR (DMSO-d6) δ: of 1.42 (9H, c)4,06 (2H, d, J=5.4 Hz), with 5.22 (2H, c), the 5.45 (2H, user. c), 7,13-of 7.23 (2H, m), 7,26-7,34 (2H, m), 7,42-7,51 (2H, m), 7,54-of 7.60 (1H, m), 7,95 (2H, c), 8,54 (1H, c).

(iii) Obtain tert-butyl[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]methylcarbamate

A mixture of tert-butyl(3-[5-amino-6-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)pyrimidine-4-yl]prop-2-vinylcarbazole (720 mg) and copper iodide(I) (55,2 mg) in N,N-dimethylformamide (7.0 ml) was stirred at 80°C for 12 hours After preconcentration with onigen the m pressure, the residue was separated and purified column chromatography (basic silica gel, eluent: ethyl acetate→methanol:ethyl acetate=1:9) to obtain the specified title compound (604 mg) as pale yellow powdery crystals.

1H-NMR (DMSO-d6) δ: of 1.42 (9H, c)to 4.33 (2H, d, J=5.7 Hz), with 5.22 (2H, c), of 6.29 (1H, c), 7,14-to 7.35 (4H, m), 7,41-of 7.60 (3H, m), 8,16 (1H, d, J=2.7 Hz), 8,30 (1H, c), 9,29 (1H, c), 10,96 (1H, user. c).

(iv) Obtaining dihydrochloride 6-(aminomethyl)-N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

To a solution of tert-butyl[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]methylcarbamate (500 mg) in tetrahydrofuran (12 ml) was added 2n. hydrochloric acid (6.0 ml) at room temperature. The mixture was stirred at 60°C for 2 h, ethanol was added to the reaction mixture and the mixture was concentrated under reduced pressure. The obtained crystals were separated by filtration and washed with diisopropyl ether to obtain specified in the connection header (481,4 mg) as pale yellow powdery crystals.

1H-NMR (DMSO-d6) δ: 4,28-4,39 (2H, m), 5,28 (2H, c), 6,89 (1H, c), 7,15-of 7.25 (1H, m), 7,29-7,40 (3H, m), 7,45-rate of 7.54 (1H, m), 7,73-7,80 (1H, m), 8,15 (1H, c), 8,48-8,65 (3H, m), 8,82 (1H, c).

Example 82

Obtain (2E)-N-{[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]methyl}-4-(dimethylamino)but-2-enamide

A solution of dihydrochloride 6-(aminomethyl)-N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5H-Pirro is about[3,2-d]pyrimidine-4-amine (150 mg), hydrochloride (2E)-4-(dimethylamino)but-2-ene acid (105 mg), the hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (244 mg), monohydrate of 1-hydroxybenzotriazole (196 mg) and triethylamine (0,30 ml) in N,N-dimethylformamide (5 ml) was stirred at room temperature for 2 days. To the reaction mixture were added water and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over magnesium sulfate, concentrated under reduced pressure, the residue was separated and purified column chromatography (basic silica gel, eluent: methanol:ethyl acetate=1:9→1:4) to obtain specified in the connection header (104,2 mg) as pale-brown powder crystals.

1H-NMR (DMSO-d6) δ: 2,14 (6H, c)of 3.00 (2H, d, J=6,1 Hz), of 4.54 (2H, d, J=5.7 Hz), to 5.21 (2H, c), 6,11 (1H, d, J=15.3 Hz), 6.35mm (1H, c), of 6.66 (1H, dt, J=15,3 and 6.1 Hz), 7,12-7,34 (4H, m), 7,41-7,49 (1H, m), 7,53-of 7.60 (1H, m), to 8.14 (1H, d, J=2.4 Hz), 8,29 (1H, c), 8,69 (1H, t, J=5.7 Hz), 9,34 (1H, user. c)10,99 (1H, user. c).

Example 83

Getting 6-(3-AMINOPHENYL)-N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

(i) Obtaining 6-[(3-AMINOPHENYL)ethinyl]-N4-{3-chloro-4-[(3-terbisil)oxy]phenyl}pyrimidine-4,5-diamine

Specified in the title compound (1.35 g) was obtained as brown powder crystals by the interaction is similar to the method of example 81 (ii)used is of N4-{3-chloro-4-[(3-terbisil)oxy]phenyl}-6-iodopyrimidine-4,5-diamine (1,90 g), 3-aminophenylacetylene (0,41 ml)dichloride bis(triphenylphosphine)palladium(II) (102 mg), copper iodide(I) (27 mg), acetonitrile (24 ml) and triethylamine (18 ml).

1H-NMR (CDCl3) δ: 3,65-of 3.78 (4H, m), 5,15 (2H, c), 6,59 (1H, c), of 6.73 (1H, d, J=8.1 Hz), 6.90 to-7,06 (4H, m), 7,14-7,41 (5H, m), 7,68 (1H, d, J=2.7 Hz), 8,35 (1H, c).

(ii) Obtaining 6-(3-AMINOPHENYL)-N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

Specified in the title compound (673 mg) was obtained as brown powder crystals by the interaction is similar to the method of example 81 (iii), using 6-[(3-AMINOPHENYL)ethinyl]-N4-{3-chloro-4-[(3-terbisil)oxy]phenyl}pyrimidine-4,5-diamine (1,30 g), copper iodide(I) (54 mg) and N,N-dimethylformamide (7.0 ml).

1H-NMR (DMSO-d6) δ: 5,23 (2H, c), 5,31 (2H, c), 6,58-of 6.65 (1H, m), of 6.75 (1H, c), 6,94-7,01 (2H, m), 7,13-7,34 (5H, m), 7,43-7,50 (1H, m), EUR 7.57 (1H, DD, J=8,9, and 2.6 Hz), 8,19 (1H, d, J=2.1 Hz), 8,32 (1H, c), 9,13 (1H, c), 11,40 (1H, c).

Example 84

Obtain N-{3-[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]phenyl}-2-methoxyacetate

Specified in the header connection (42.9 mg) was obtained as pale-brown powder crystals by the interaction is similar to the method of example 82, using 6-(3-AMINOPHENYL)-N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine (80 mg), methoxybutanol acid (31 mg), hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)ka is bodiimide (67 mg), monohydrate of 1-hydroxybenzotriazole (54 mg), triethylamine (0.1 ml) and N,N-dimethylformamide (5 ml).

1H-NMR (DMSO-d6) δ: 3,42 (3H, c)4,06 (2H, c), of 5.24 (2H, c), 6,87 (1H, c), 7,13 and 7.36 (4H, m), 7,44-of 7.69 (5H, m), 8,19 compared to 8.26 (2H, m), 8,35 (1H, c), a 9.25 (1H, c), for 9.95 (1H, c), to 11.56 (1H, c).

Example 85

Getting 6-(4-AMINOPHENYL)-N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

(i) Obtaining 6-[(4-AMINOPHENYL)ethinyl]-N4-{3-chloro-4-[(3-terbisil)oxy]phenyl}pyrimidine-4,5-diamine

Specified in the title compound (1.12 g) was obtained as yellow solid interaction similar to the method of example 81 (ii)using N4-{3-chloro-4-[(3-terbisil)oxy]phenyl}-6-iodopyrimidine-4,5-diamine (1.50 g), 4-aminophenylacetylene (411 mg)dichloride bis(triphenylphosphine)palladium(II) (112 mg), copper iodide(I) (36,5 mg), acetonitrile (24 ml) and triethylamine (18 ml).

1H-NMR (CDCl3) δ: 3,68 (2H, user. c)of 3.94 (2H, user. c)5,14 (2H, c), to 6.58 (1H, user. c)of 6.65 (2H, d, J=7.8 Hz), to 6.95 (1H, d, J=9.0 Hz), of 6.96-7,06 (1H, m), 7,19-the 7.43 (6H, m), 7,68 (1H, d, J=2.7 Hz), a 8.34 (1H, c).

(ii) Obtaining 6-(4-AMINOPHENYL)-N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

Specified in the header connection (768,6 mg) was obtained as a yellow powdery crystals the interaction is similar to the method of example 81 (iii), using 6-[(4-AMINOPHENYL)ethinyl]-N4-{3-chloro-4-[(3-terbisil)oxy]phenyl}pyrimidine-4,5-Diame is a (1,11 g), iodide copper(I) - (46 mg) and N,N-dimethylformamide (6.0 ml).

1H-NMR (DMSO-d6) δ: 5,22 (2H, c), of 5.53 (2H, c), 6,65-6,70 (3H, m), 7,12-to 7.35 (4H, m), 7,42-to 7.61 (4H, m), 8,17 (1H, d, J=2.7 Hz), of 8.28 (1H, c), 8,99 (1H, c), 11,21 (1H, user. c).

Example 86

Obtain N-{4-[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]phenyl}-2-methoxyacetate

A solution of 6-(4-AMINOPHENYL)-N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine (100 mg), methoxybutanol acid (to 29.4 mg), hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (94 mg), monohydrate of 1-hydroxybenzotriazole (75 mg) and triethylamine (0,23 ml) in N,N-dimethylformamide (5 ml) was stirred at room temperature within 20 hours Methoxybutanol acid (to 29.4 mg), hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (94 mg) and the monohydrate of 1-hydroxybenzotriazole (75 mg) was added to the reaction system and the mixture was additionally stirred for 24 hours Water was added to the reaction system and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over magnesium sulfate, concentrated under reduced pressure, the residue was separated and purified column chromatography (basic silica gel, eluent: ethyl acetate→methanol:ethyl acetate=14:85) to obtain specified in the connection header (63.5 mg) as pale-brown powder the crystals.

1H-NMR (DMSO-d6) δ: 3.40 in (3H, c), Android 4.04 (2H, c), 5,23 (2H, c), of 6.90 (1H, c), 7,12-7,21 (1H, m), 7.23 percent-of 7.35 (3H, c), 7,43-7,49 (1H, m), 7,52-of 7.60 (1H, m), 7,78-7,87 (4H, m), 8,19 (1H, d, J=1,8 Hz), with 8.33 (1H, c), 9,07 (1H, c), becomes 9.97 (1H, c), of 11.45 (1H, c).

Example 87

Obtain (2E)-3-[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]prop-2-en-1-ol

(i) Obtain (2E)-5-[5-amino-6-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)pyrimidine-4-yl]Penta-2-EN-4-in-1-ol

Specified in the header connection (188,2 mg) was obtained as a brown solid interaction similar to the method of example 81 (ii)using N4-{3-chloro-4-[(3-terbisil)oxy]phenyl}-6-iodopyrimidine-4,5-diamine (300 mg), 2-penten-4-in-1-ol (58 mg)dichloride bis(triphenylphosphine)palladium(II) are (22.5 mg), copper iodide(I) (7,3 mg), acetonitrile (6,0 ml) and triethylamine (4.5 ml).

1H-NMR (DMSO-d6) δ: 4,06-to 4.15 (2H, m), is 5.06 (1H, t, J=5.4 Hz), to 5.21 (2H, c), the 5.45 (2H, user. c)5,98-6,07 (1H, m), 6,46-to 6.57 (1H, m), 7,12-7,34 (4H, m), 7,39-to 7.59 (2H, m), 7,92-to 7.99 (2H, m), 8,55 (1H, user. c).

(ii) Obtain (2E)-3-[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]prop-2-EN-1-ol

Specified in the title compound (98 mg) was obtained as pale yellow powdery crystals the interaction is similar to the method of example 81 (iii), using (2E)-5-[5-amino-6-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)pyrimidine-4-yl]Penta-2-EN-4-in-1-ol (170 mg), copper iodide(I) (7,6 mg)and N,N-dimethylformamide (1.5 ml).

1H-NMR (DMSO-d6) δ: 4,16-4,24 (2H, m), 5,02-5,09 (1H, m), with 5.22 (2H, c), 6,40-of 6.52 (2H, m), of 6.66 (1H, d, J=15,9 Hz), 7,13-7,34 (4H, m), 7,41-7,50 (1H, m), 7,52-of 7.60 (1H, m), 8,17 (1H, d, J=2.7 Hz), 8,29 (1H, c), 9,13 (1H, user. c), 11,38 (1H, user. c).

Example 88

Obtain 3-[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]propan-1-ol

(i) Obtain 5-[5-amino-6-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)pyrimidine-4-yl]Penta-4-in-1-ol

To a solution of N4-{3-chloro-4-[(3-terbisil)oxy]phenyl}-6-iodopyrimidine-4,5-diamine (300 mg) and 4-pentyn-1-ol (65 mg) in a mixture of acetonitrile-triethylamine (6.0 ml to 4.5 ml) was added dichloride bis(triphenylphosphine)palladium(II) (22,5 mg) and copper iodide(I) (7,3 mg) at room temperature and the mixture was stirred at room temperature in an argon atmosphere for 24 hours 4-Penten-1-ol (65 mg)dichloride bis(triphenylphosphine)palladium(II) (22,5 mg) and copper iodide(I) (7,3 mg) was added to the reaction system and the mixture was stirred at 60°C for 2 hours After concentration under reduced pressure the residue was separated and purified column chromatography (basic silica gel, eluent: ethyl acetate→methanol:ethyl acetate=1:19) to obtain specified in the connection header (157,2 mg) as a yellow solid.

1H-NMR (DMSO-d6) δ: 1,66-to 1.79 (2H, m), 2,43-of 2.58 (2H, m), 3,53 (2H, q, J=5.4 Hz), br4.61 (1H, t, J=5,1 Hz), 5,20 (2H, c), 5,31 (2H, c), 7,11-7,21 (2H, m), 7,25-7,33 (2H, m), 7,39-7,50 (1H, m), 7,55 (1H, DD, J=9,0, 2.1 Hz), 7,9-7,94 (2H, m), and 8.50 (1H, c).

(ii) Obtain 3-[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]propan-1-ol

A mixture of 5-[5-amino-6-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)pyrimidine-4-yl]Penta-4-in-1-ol (140 mg) and copper iodide(I) (19 mg) in N,N-dimethylformamide (2.0 ml) was stirred at 80°C for 5 hours After concentration under reduced pressure the residue was separated and purified column chromatography (basic silica gel, eluent: ethyl acetate→methanol:ethyl acetate=15:85) to obtain specified in the connection header (for 95.2 mg) as pale-brown powder crystals.

1H-NMR (DMSO-d6) δ: 1,79 is 1.91 (2H, m), 2,84 (2H, t, J=7.8 Hz), 3,44-to 3.52 (2H, m), 4,62-and 4.68 (1H, m), with 5.22 (2H, c), 6,24 (1H, c), 7,13-to 7.35 (4H, m), 7,43-to 7.59 (2H, m), 8,17 (1H, d, J=2.7 Hz), 8,29 (1H, c), 9,01 (1H, user. c)10,94 is 11.05 (1H, m).

Example 89

Getting 4-[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]butane-1-ol

(i) Obtaining 6-[5-amino-6-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)pyrimidine-4-yl]Gex-5-in-1-ol

Specified in the title compound (242 mg) was obtained as a brown solid interaction similar to the method of example 81 (ii)using N4-{3-chloro-4-[(3-terbisil)oxy]phenyl}-6-iodopyrimidine-4,5-diamine (300 mg), 5-hexyne-1-ol (94,2 mg)dichloride bis(triphenylphosphine)palladium(II) are (22.5 mg), copper iodide(I) (7,3 mg), acetonitrile (6.0 ml) and tree is ylamine (4,5 ml).

1H-NMR (DMSO-d6) δ: 1,51 was 1.69 (4H, m), 2,39-of 2.58 (2H, m), 3,41-3,47 (2H, m), 4,46 (1H, t, J=4,8 Hz), 5,20 (2H, c), 5,28 (2H, user. c), 7,12-7,22 (2H, m), 7,25-7,33 (2H, m), 7,41-7,49 (1H, m), 7,55 (1H, DD, J=8,6, 2,9 Hz), 7,89-of 7.96 (2H, m), and 8.50 (1H, c).

(ii) Obtaining 4-[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]butane-1-ol

Specified in the title compound (109 mg) was obtained as pale-brown powder crystals by the interaction is similar to the method of example 81 (iii), using 6-[5-amino-6-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)pyrimidine-4-yl]Gex-5-in-1-ol (220 mg), copper iodide(I) (9.5 mg) and N,N-dimethylformamide (4.0 ml).

1H-NMR (DMSO-d6) δ: 1,44-of 1.56 (2H, m), 1,67-of 1.81 (2H, m), 2,80 (2H, t, J=7.8 Hz), of 3.45 (2H, t, J=6.0 Hz), 4,40-4,50 (1H, m), a total of 5.21 (2H, c), from 6.22 (1H, c), 7,12-to 7.32 (4H, m), 7,42-of 7.55 (2H, m), 8,15 (1H, d, J=2.7 Hz), 8,27 (1H, c), 8,98 (1H, c), of 10.93 (1H, user. c).

Example 90

Obtain 6-[(1E)-3-aminopropan-1-enyl]-N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

(i) Obtaining tert-butyl(2E)-5-[5-amino-6-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)pyrimidine-4-yl]Penta-2-EN-4-vinylcarbazole

Specified in the header connection (373,8 mg) was obtained as yellow solid interaction similar to the method of example 81 (ii)using N4-{3-chloro-4-[(3-terbisil)oxy]phenyl}-6-iodopyrimidine-4,5-diamine (600 mg), tert-Butrint-2-EN-4-vinylcarbazole (0.26 g), dichloride bis(three is edelfosine)palladium(II) (44,6 mg), iodide copper(I) (14,5 mg), acetonitrile (12 ml) and triethylamine (9 ml).

1H-NMR (DMSO-d6) δ: of 1.40 (9H, c), 3,66 of 3.75 (2H, m), a total of 5.21 (2H, c), 5,49 (2H, user. c)5,91 (1H, d, J=10,2 Hz), 6.30-in-6.42 per (1H, m), 7,12-of 7.25 (3H, m), 7,27 was 7.36 (2H, m), 7,42-7,51 (1H, m), 7,54 to 7.62 (1H, m), 7,93-to 7.99 (2H, m), 8,58 (1H, c).

(ii) Obtain tert-butyl(2E)-3-[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]prop-2-talkabout

Specified in the title compound (189 mg) was obtained as pale-brown powder crystals by the interaction is similar to the method of example 81 (iii)using tert-butyl(2E)-5-[5-amino-6-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)pyrimidine-4-yl]Penta-2-EN-4-vinylcarbazole (350 mg), copper iodide(I) (12,7 mg) and N,N-dimethylformamide (2.0 ml).

1H-NMR (DMSO-d6) δ: of 1.41 (9H, c), of 3.73-of 3.85 (2H, m), 5,23 (2H, c), 6,22-6,36 (1H, m), 6.48 in-6,62 (2H, m), 7,14-7,38 (5H, m), 7,42-7,50 (1H, m), 7,52 to 7.62 (1H, m), 8,18 (1H, c), 8,30 (1H, c), 9,06 (1H, user. c), of 11.29 (1H, user. c).

(iii) Obtaining 6-[(1E)-3-aminopropan-1-enyl]-N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

To a solution of tert-butyl(2E)-3-[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]prop-2-talkabout (150 mg) in tetrahydrofuran (6.0 ml) was added 2n. hydrochloric acid (3.0 ml) at room temperature and the mixture was stirred at 60°C for 2 hours was Added 1N. an aqueous solution of sodium hydroxide for alkalizing the reaction system. After extrage the Finance with chloroform, the organic layer was dried over sodium sulfate and concentrated under reduced pressure. The obtained crystals were separated by filtration. The crystals are washed with diisopropyl ether to obtain specified in the title compound (104 mg) as pale-brown powder crystals.

1H-NMR (DMSO-d6) δ: 3,42 (2H, d, J=4, 2 Hz), with 5.22 (2H, c), 6,41-6,50 (2H, m), 6,62 (1H, d, J=15,9 Hz), 7,12-to 7.35 (4H, m), 7,42-7,50 (1H, m), EUR 7.57-of 7.60 (1H, m), 8,18 (1H, d, J=2.1 Hz), of 8.28 (1H, c), 9,20 (1H, user. c), is 11.39 (1H, user. c).

Example 91

Obtain N-{(2E)-3-[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-6-yl]prop-2-enyl}-2-methoxyacetate

Specified in the header connection (23,2 mg) was obtained as pale-brown powder crystals by the interaction is similar to the method of example 82, using 6-[(1E)-3-aminopropan-1-enyl]-N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine (30 mg), methoxybutanol acid (14 mg), hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (55 mg), monohydrate of 1-hydroxybenzotriazole (44 mg), triethylamine (0.1 ml) and N,N-dimethylformamide (5 ml).

1H-NMR (DMSO-d6) δ: 3,34 (3H, c), a 3.87 (2H, c), of 3.95 (2H, t, J=5.4 Hz), to 5.21 (2H, c), 6.35mm (1H, dt, J=16,2, 5.7 Hz), 6,47 (1H, c), 6,56 (1H, d, J=16.2 Hz), 7,12-to 7.32 (4H, m), 7,41-7,50 (1H, m), a 7.62 (1H, DD, J=9,0, 2.7 GHz), 8,16 is 8.25 (2H, m), of 8.28 (1H, c), 9,37-9,52 (1H, m), 11,67-11,84 (1H, m).

Example 92

Obtain (2E)-N-{(2E)-3-[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]p is rimidine-6-yl]prop-2-enyl}-4-(dimethylamino)but-2-enamide

Specified in the title compound (25.6 mg) was obtained as pale yellow powdery crystals the interaction is similar to the method of example 82, using 6-[(1E)-3-aminopropan-1-enyl]-N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine (40 mg), hydrochloride (2E)-4-(dimethylamino)but-2-ene acid (31 mg), hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (72 mg), monohydrate of 1-hydroxybenzotriazole (58 mg), triethylamine (0,13 ml) and N,N-dimethylformamide (5 ml).

1H-NMR (DMSO-d6) δ: 2,15 (6H, c)of 3.00 (2H, d, J=6.3 Hz), 3,97-4,06 (2H, m), 5,23 (2H, c), 6,10 (1H, d, J=15.3 Hz), 6,27-6,40 (1H, m), 6,51 (1H, c), 6,55 of 6.68 (2H, m), 7,14 and 7.36 (4H, m), 7,43-of 7.60 (2H, m), 8,17 (1H, d, J=2.7 Hz), 8,31 (1H, c), to 8.41-to 8.45 (1H, m), 9,01 (1H, c), 11,22 (1H, c).

Example 93

Getting 2-{[2-chloro-4-(5H-pyrrolo[3,2-d]pyrimidine-4-ylamino)phenoxy]methyl}benzonitrile

Specified in the title compound (272 mg) was obtained by interaction similar to the method of example 2 (ii)using 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (200 mg) and 2-[(4-amino-2-chlorophenoxy)methyl]benzonitrile (337 mg).

1H-NMR (DMSO-d6) δ 5,33 (2H, c), of 6.49 (1H, c), 7,32 (1H, d, J=9.0 Hz), EUR 7.57-to 7.68 (3H, m), 7,78-7,80 (2H, m), 7,94 (1H, d, J=8.1 Hz), to 8.20 (1H, m), at 8.36 (1H, c), to 9.32 (1H, user. c)and 11.1 (1H, user. c).

Example 94

Obtain 3-[2-methyl-4-(5H-pyrrolo[3,2-d]pyrimidine-4-ylamino)phenoxy]benzonitrile

Specified in the header is the compound (338 mg) was obtained by interaction similar to the method of example 2 (ii), using 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (200 mg) and 3-(4-amino-2-methylphenoxy)benzonitrile (292 mg).

1H-NMR (DMSO-d6) δ of 2.16 (3H, c), of 6.49 (1H, c), 7,06 (1H, d, J=9.3 Hz), 7,21 (1H, m), 7,35 (1H, c), 7,51-to 7.59 (2H, m), 7,69 (1H, m), 7,80-7,83 (2H, m), 8,35 (1H, c), 9,26 (1H, c)and 11.1 (1H, user. c).

Example 95

Obtain 3-[2-chloro-4-(5H-pyrrolo[3,2-d]pyrimidine-4-ylamino)phenoxy]benzonitrile

Specified in the title compound (230 mg) was obtained by interaction similar to the method of example 2 (ii)using 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (150 mg) and 3-(4-amino-2-chlorophenoxy)benzonitrile (219 mg).

1H-NMR (DMSO-d6) δ 6,53 (1H, c), 7,26 (1H, m), 7,32 (1H, d, J=8.7 Hz), 7,45 (1H, c), 7,58 (2H, d, J=5.7 Hz), 7,70-7,73 (2H, m), to 8.41 (2H, c), 9,50 (1H, c)and 11.1 (1H, user. c).

Example 96

Getting 2-{[2-methyl-4-(5H-pyrrolo[3,2-d]pyrimidine-4-ylamino)phenoxy]methyl}benzonitrile

Specified in the title compound (250 mg) was obtained by interaction similar to the method of example 2 (ii)using 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (200 mg) and 2-[(4-amino-2-methylphenoxy)methyl]benzonitrile (310 mg).

1H-NMR (DMSO-d6) δ of 2.24 (3H, c), of 5.26 (2H, c), 6,46 (1H, t, J=1.5 Hz), was 7.08 (1H, d, J=9.0 Hz), 7,58-to 7.68 (4H, m), 7,78 (2H, d, J=4, 2 Hz), 7,94 (1H, d, J=7.5 Hz), 8,29 (1H, c), of 9.02 (1H, user. c)and 11.1 (1H, user. c).

Example 97

Obtain N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-1H-pyrazolo[4,-d]pyrimidine-7-amine

A mixture of 7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidine (known from the literature connection:J. Am. Chem. Soc., 1956, 78, 2418) (150 mg), 3-chloro-4-[(3-terbisil)oxy]aniline (227 mg) and pyridine hydrochloride (156 mg) in 1-methyl-2-pyrrolidone (3 ml) was stirred at 120°C for 10 h after the reaction mixture was diluted with ethyl acetate and washed with saturated aqueous sodium hydrogen carbonate solution and saturated salt solution. The organic layer was concentrated under reduced pressure and the residue was subjected to chromatography on a column of silica gel (hexane/ethyl acetate=1/3→1/10) to obtain the specified title compound (220 mg, yield 61%) as a pale yellow solid.

1H-NMR (CDCl3) δ of 5.15 (2H, c), of 6.96 (1H, d, J=8.7 Hz), 7,03 (1H, m), 7,20-7,26 (2H, m), of 7.36 (1H, dt, J=5,7, and 8.4 Hz), 7,71 (1H, DD, J=2.7, and 9.0 Hz), 7,81 (1H, d, J=2.7 Hz), 8,14 (1H, c), to 8.57 (1H, c).

Example 98

Obtain N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-1H-pyrazolo[4,3-d]pyrimidine-7-amine

Specified in the title compound (195 mg) was obtained as a brown solid interaction similar to the method of example 97 using 7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidine (150 mg), 3-methyl-4-[(6-methylpyridin-3-yl)oxy]aniline (193 mg) and pyridine hydrochloride (156 mg).

1H-NMR (CDCl3) δ a 2.13 (3H, c), 6,89 (1H, d, J=8,4 Hz), 7,11 (1H, d, J=8.1 Hz), to 7.15 (1H, DD, J=2.7, and an 8.4 Hz), to 7.50 (1H, DD, J=2.7, and 9.0 Hz), 7,68 (1H, is, J=2.7 Hz), 8,14 (1H, c), of 8.25 (1H, d, J=2.7 Hz), 8,58 (1H, c).

Example 99

Getting 4-{[7-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-1H-pyrazolo[4,3-d]pyrimidine-1-yl]methyl}methylbenzoate

Specified in the title compound (45 mg) was obtained as a brown solid interaction similar to the method of example 97, using 4-{[7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidine-1-yl]methyl}methylbenzoate (120 mg), 3-chloro-4-[(3-terbisil)oxy]aniline (87 mg) and pyridine hydrochloride (60 mg).

1H-NMR (CDCl3) δ of 3.94 (3H, c), 5,11 (2H, c), 5,90 (2H, c), 6,34 (1H, user. c), 6,85 (1H, d, J=8.7 Hz), 6,94 (1H, DD, J=2.7, and 8.7 Hz), 7,01 (1H, m), 7,16-7,22 (2H, m), 7,32 (2H, d, J=8.7 Hz), 7,35 (1H, m)to 8.14 (2H, d, J=8.7 Hz), 8,18 (1H, c), 8,51 (1H, c).

Example 100

Getting 4-{[7-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]methyl}methylbenzoate

Specified in the title compound (140 mg) was obtained as a pale yellow solid interaction by the similar method of example 97, using 4-{[7-(methylthio)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]methyl}methylbenzoate (150 mg), 3-chloro-4-[(3-terbisil)oxy]aniline (109 mg) and pyridine hydrochloride (75 mg).

1H-NMR (CDCl3) δ to 3.92 (3H, c), 5,16 (2H, c), 5,62 (2H, c), 6,97 (1H, d, J=8,8 Hz), 7,02 (1H, m), 7.18 in-7,42 (4H, m), 7,55-to 7.68 (2H, m), 8,00-8,08 (4H, m), and 8.50 (1H, c).

Example 101

Getting 4-{[7-(3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-1H-pyrazolo[4,3-d]pyrimidine-1-yl]methyl}benzoic acid

To a solution of 4-{[7-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-1H-pyrazolo[4,3-d]pyrimidine-1-yl]methyl}methylbenzoate (25 mg) in a mixed solvent of tetrahydrofuran-methanol (1:1, 1 ml) was added 1N. an aqueous solution of sodium hydroxide (0.5 ml) and the mixture was stirred at room temperature for 1 h after the reaction of 1H. an aqueous solution of hydrochloric acid (0.5 ml) and water (1 ml) was added under ice cooling and the mixture was stirred at room temperature for 1 h resulting solid substance was separated by filtration, washed with diisopropyl ether and dried to obtain specified in the title compound (16 mg) as pale-yellow crystals.

1H-NMR (DMSO-d6) ∆ 5,24 (2H, c), 6,10 (2H, c), 7,13-7,31 (5H, m), 7,42-7,47 (2H, m), of 7.70 (1H, m), 7,83-to $ 7.91 (2H, m), of 8.27 (1H, c), 8,35 (1H, c), 8,81 (1H, c), and 12.9 (1H, user. c).

Example 102

Getting 4-{[7-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]methyl}benzoic acid

Specified in the title compound (130 mg) was obtained as pale-yellow crystals by the interaction is similar to the method of example 101, using 4-{[7-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]methyl}methylbenzoate (150 mg) and 1H. an aqueous solution of sodium hydroxide (6 ml).

1H-NMR (DMSO-d6) δ of 5.26 (2H, c), to 5.85 (2H, c), 7,15-to 7.32 (4H, m), 7,41 (2H, d, J=8.1 Hz), 7,45 (1H, is), 7,72 (1H, DD, J=2,4, and 8.7 Hz), 7,94 (2H, d, J=8.1 Hz), of 8.06 (1H, d, J=2.1 Hz), 8,65 (1H, c), cent to 8.85 (1H, c), and 11.4 (1H, user. c).

Example 103

Getting 4-{[7-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-1H-pyrazolo[4,3-d]pyrimidine-1-yl]methyl}benzoic acid

4-{[7-({3-Methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-1H-pyrazolo[4,3-d]pyrimidine-1-yl]methyl}methylbenzoate received in the form of a mixture with 1-methyl-2-pyrrolidone interaction similar to the method of example 97, using 4-{[7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidine-1-yl]methyl}methylbenzoate (120 mg), 3-methyl-4-[(6-methylpyridin-3-yl)oxy]aniline (87 mg) and pyridine hydrochloride (60 mg).

Specified in the title compound (20 mg) was obtained as yellow crystals by the interaction is similar to the method of example 101, using the above mixture and 1H. an aqueous solution of sodium hydroxide (1 ml).

1H-NMR (DMSO-d6) δ 2,17 (3H, c), 2,43 (3H, c), 6,12 (2H, c)6,91 (2H, d, J=8.7 Hz), 7,12-7,24 (4H, m), 7,38-7,47 (2H, m), a 7.85 (2H, d, J=8.1 Hz), 8,16 (1H, d, J=2.4 Hz), of 8.28 (1H, c), 8,35 (1H, c), 8,81 (1H, c).

Example 104

Getting 4-{[7-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]methyl}methylbenzoate

Specified in the title compound (160 mg) was obtained as pale-yellow crystals by the interaction is similar to the method of example 97, using 4-{[7-(methylthio)-2H-pyrazole is[4,3-d]pyrimidine-2-yl]methyl}methylbenzoate (150 mg), 3-methyl-4-[(6-methylpyridin-3-yl)oxy]aniline (93 mg) and pyridine hydrochloride (75 mg).

1H-NMR (CDCl3) δ of 2.27 (3H, c), 2,52 (3H, c), 3,91 (3H, c), the ceiling of 5.60 (2H, c), of 6.90 (1H, d, J=8.7 Hz), 7,08-to 7.09 (2H, m), 7,31 (1H, c), 7,66 (1H, DD, J=3,0, 9.0 Hz), 7,76 (1H, d, J=2.4 Hz), 7,86 (1H, m), 8,02 (2H, c), 8,04 (1H, c), of 8.25 (1H, m), 8,51 (1H, c).

Example 105

Getting 4-{[7-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]methyl}benzoic acid

Specified in the title compound (120 mg) was obtained as white crystals by the interaction is similar to the method of example 101, using 4-{[7-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]methyl}methylbenzoate (150 mg) and 1H. an aqueous solution of sodium hydroxide (3 ml).

1H-NMR (DMSO-d6) δ 2,17 (3H, c), 2,43 (3H, c)5,80 (2H, c), 6,93 (1H, d, J=8.7 Hz), 7,13-of 7.23 (2H, m), 7,37 (2H, d, J=7.8 Hz), to 7.84 (1H, DD, J=2,1, 9.0 Hz), 7,92-of 7.97 (2H, m), 8,15 (1H, d, J=2.1 Hz), 8,32 (1H, c), 8,67 (1H, c), of 10.09 (1H, c), 13,0 (1H, user. c).

Example 106

Getting 4-{[7-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]methyl}-N-(2-methoxyethyl)benzamide

A solution of 4-{[7-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]methyl}benzoic acid (45 mg), 2-methoxyethylamine (9 mg), 1-hydroxybenzotriazole (18 mg), the hydrochloride of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (26 mg) and triethylamine (0,08 ml) is N,N-dimethylformamide (2 ml) was stirred at room temperature for 30 hours Upon completion of the reaction, the reaction solution was concentrated under reduced pressure and the residue was subjected to chromatography on a column of silica gel (basic silica gel; ethyl acetate) to obtain the specified title compound (115 mg) as a pale yellow solid.

1H-NMR (CDCl3) δ to 3.38 (3H, c), 3,54 is 3.57 (2H, m), 3,63-3,68 (2H, m), 5,12 (2H, c), the ceiling of 5.60 (2H, c), 6,53 (1H, user. c), 6,97 (1H, d, J=8.7 Hz), 7,02 (1H, m), 7,20-7,40 (3H, m), 7,31 (1H, d, J=8,4 Hz), to 7.64 (1H, d, J=8.7 Hz), the 7.65 (1H, d, J=8,4 Hz), 7,79 (1H, d, J=8,4 Hz), 8,00 shed 8.01 (2H, m), and 8.50 (1H, c).

Example 107

Obtaining N-(2-methoxyethyl)-4-{[7-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]methyl}benzamide

Specified in the title compound (30 mg) was obtained as white crystals by the interaction is similar to the method of example 106 using 4-{[7-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]methyl}benzoic acid (45 mg), 2-methoxyethylamine (10 mg), 1-hydroxybenzotriazole (20 mg), hydrochloride of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (28 mg) and triethylamine (0,08 ml).

1H-NMR (CDCl3) δ to 2.29 (3H, c), of 2.53 (3H, c), to 3.38 (3H, c), 3,54 is 3.57 (2H, m), 3,63-3,68 (2H, m), 5,62 (2H, c), 6,51 (1H, user. c)6,93 (1H, d, J=8.7 Hz), 7,09-7,10 (2H, m), 7,34 (2H, d, J=8.1 Hz), 7,62-of 7.69 (2H, m), 7,76 (1H, m), 7,80 (1H, d, J=8.1 Hz), 8,02 (1H, c), compared to 8.26 (1H, m), 8,51 (1H, c).

Example 108

Obtain N-{3-meth is l-4-[(6-methylpyridin-3-yl)oxy]phenyl}-2-(4-nitrophenyl)-2H-pyrazolo[4,3-d]pyrimidine-7-amine

(i) produce 7-(methylthio)-2-(4-nitrophenyl)-2H-pyrazolo[4,3-d]pyrimidine

To a solution of 7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidine (500 mg) in N,N-dimethylformamide (10 ml) was added tert-piperonyl potassium (405 mg) under ice cooling and the mixture was stirred at room temperature for 10 minutes and Then was added 1-fluoro-4-nitrobenzene (465 mg) and the mixture was stirred at 70°C for 30 minutes after the reaction was added water to the reaction mixture and the mixture was stirred at room temperature for 30 minutes resulting solid substance was separated by filtration off , washed with diisopropyl ether and dried to obtain specified in the title compound (860 mg) as brown crystals.

1H-NMR (DMSO-d6) δ of 2.72 (3H, c), 8,39 (2H, d, J=8.7 Hz), 8,46 (2H, d, J=8.7 Hz), 8,76 (1H, c), for 9.64 (1H, c).

(ii) Obtaining N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-2-(4-nitrophenyl)-2H-pyrazolo[4,3-d]pyrimidine-7-amine

Specified in the title compound (667 mg) was obtained as a pale yellow solid interaction by the similar method of example 97 using 7-(methylthio)-2-(4-nitrophenyl)-2H-pyrazolo[4,3-d]pyrimidine (430 mg), 3-methyl-4-[(6-methylpyridin-3-yl)oxy]aniline (321 mg) and pyridine hydrochloride (259 mg).

1H-NMR (CDCl3) δ 2,32 (3H, c), of 2.54 (3H, c), to 6.95 (1H, d, J=9.0 Hz), 7,07-to 7.15 (2H, m), 7,71 (1H, DD, J=2.7, and an 8.4 Hz), 7,80-7,81 (2H, m)to 8.12 (2H, d, J=9.3 Hz), of 8.25 (1H, DD, J=0,6, 2.7 Hz), to 8.45 (2H, d, J=9.3 Hz), 8,55 (1H, c), and 8.5 (1H, c).

Example 109

Obtaining 2-(4-AMINOPHENYL)-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-2H-pyrazolo[4,3-d]pyrimidine-7-amine

To a solution of N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-2-(4-nitrophenyl)-2H-pyrazolo[4,3-d]pyrimidine-7-amine (200 mg) in a mixed solvent of ethanol-water (9:1, 6 ml) was added calcium chloride (90%, 28 mg) and the mixture was stirred at 100°C for 10 minutes reduced iron (90%, 164 mg) was added at room temperature and the mixture was stirred at 100°C for 5 hours Upon completion of the reaction, the reaction mixture was filtered (celite) and the filtrate was concentrated under reduced pressure. To the residue was added water, the mixture was diluted with ethyl acetate and washed with water and saturated salt solution. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (ethyl acetate/methylene chloride=10/1) to obtain the specified title compound (140 mg) as a white solid.

1H-NMR (DMSO-d6) δ of 2.20 (3H, c), is 2.44 (3H, c), of 5.55 (2H, c), of 6.71-6,74 (2H, m), 6,95-6,98 (1H, m), 7.18 in-of 7.23 (2H, m), 7,73-7,76 (2H, m)7,901 (1H, m), 8,03 (1H, user. c), 8,18 (1H, user. c)to 8.34 (1H, user. c)to 8.94 (1H, user. c), of 10.05 (1H, user. c).

Example 110

Getting 2-methoxy-N-{4-[7-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-2H-feast of the olo[4,3-d]pyrimidine-2-yl]phenyl}ndimethylacetamide

Specified in the title compound (64 mg) was obtained as white crystals by the interaction is similar to the method of example 106 using 2-(4-AMINOPHENYL)-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-2H-pyrazolo[4,3-d]pyrimidine-7-amine (100 mg), methoxybutanol acid (30 mg), 1-hydroxybenzotriazole (48 mg), hydrochloride of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (68 mg) and triethylamine (0,20 ml).

1H-NMR (CDCl3) δ of 2.26 (3H, c), of 2.53 (3H, c), 3,55 (3H, c)4,07 (2H, c), 6,92 (1H, d, J=8.7 Hz), 7,12-of 7.25 (2H, m), 7,35-7,45 (3H, m), 7,70-7,83 (4H, m), 8,19 (1H, d, J=2.4 Hz), 8,44 (2H, c), and 8.50 (1H, c).

Example 111

Getting 2-(N,N-dimethylamino)-N-{4-[7-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]phenyl}ndimethylacetamide

Specified in the title compound (60 mg) was obtained as white crystals by the interaction is similar to the method of example 106 using 2-(4-AMINOPHENYL)-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-2H-pyrazolo[4,3-d]pyrimidine-7-amine (100 mg), hydrochloride N,N-dimethylglycine (46 mg), 1-hydroxybenzotriazole (48 mg), hydrochloride of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (68 mg) and triethylamine (0,20 ml).

1H-NMR (CDCl3) δ 2,31 (3H, c), 2,43 (6H, c)of 2.53 (3H, c), 3,14 (2H, c), to 6.95 (1H, d, J=9.0 Hz), 7,09-7,11 (2H, m), 7,70-7,76 (2H, m), 7,81-a 7.85 (5H, m), of 8.27 (1H, m), 8,43 (1H, c), 8,55 (1H, c), a 9.35 (1H, user. c).

Example 112

Getting 4-({-[7-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]phenyl}amino)-4-oxometabolite

Specified in the title compound (175 mg) was obtained as white crystals by the interaction is similar to the method of example 106 using 2-(4-AMINOPHENYL)-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-2H-pyrazolo[4,3-d]pyrimidine-7-amine (150 mg), nanometrology ester of succinic acid (66 mg), 1-hydroxybenzotriazole (72 mg), hydrochloride of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (102 mg) and triethylamine (0,30 ml).

1H-NMR (CDCl3) δ is 2.30 (3H, c), of 2.53 (3H, c), 2,73 is 2.75 (2H, m), 2,79-of 2.81 (2H, m in), 3.75 (3H, c)6,94 (1H, d, J=8.7 Hz), 7,10 for 7.12 (2H, m), 7,69-7,74 (3H, m), 7,79-of 7.82 (4H, m), 8,08 (1H, user. c)of 8.27 (1H, DD, J=0,6, 2.4 Hz), 8,42 (1H, c), 8,53 (1H, c).

Example 113

Getting 4-({4-[7-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]phenyl}amino)-4-oxobutanoic acid

Specified in the title compound (98 mg) was obtained as white crystals by the interaction is similar to the method of example 101, using methyl 4-({4-[7-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]phenyl}amino)-4-oxobutanoate (175 mg) and 1H. an aqueous solution of sodium hydroxide (0.5 ml).

1H-NMR (DMSO-d6) δ of 2.21 (3H, c), is 2.44 (3H, c), 2,50-2,61 (4H, m), 6,97 (1H, d, J=8,4 Hz), 7,20-7,22 (2H, m), 7,81-to 7.93 (4H, m), 8,03-of 8.09 (3H, m), 8,18 (1H, m), at 8.36 (1H, c), 9,13 (1H, c), 10,2 (1H, user. c)to 10.3 (1H, c).

Example 114

Obtaining 2-(2-methoxyethoxy)-N-{4-[7-({3-IU the Il-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]phenyl}ndimethylacetamide

Specified in the title compound (88 mg) was obtained as white crystals by the interaction is similar to the method of example 106 using 2-(4-AMINOPHENYL)-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-2H-pyrazolo[4,3-d]pyrimidine-7-amine (130 mg), (2 methoxyethoxy)acetic acid (58 mg), 1-hydroxybenzotriazole (62 mg), hydrochloride of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (88 mg) and triethylamine (0.26 per ml).

1H-NMR (CDCl3) δ is 2.30 (3H, c), of 2.53 (3H, c), 3,52 (3H, c), 3,63-3,66 (2H, m), 3,80-3,82 (2H, m)to 4.16 (2H, c)6,94 (1H, d, J=8.7 Hz), 7,07-7,10 (2H, m), 7,71 (1H, d, J=8.7 Hz), 7,80 (1H, m), 7,83 (4H, c), of 8.27 (1H, c), 8,43 (1H, c), 8,54 (1H, c), 9,16 (1H, c).

Example 115

Getting 4-[7-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]methylbenzoate

(i) Obtaining 4-[7-(methylthio)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]methylbenzoate

To a solution of 7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidine (100 mg) and 4-permitivitty (102 mg) in 1-methyl-2-pyrrolidone (2 ml) was added potassium carbonate (125 mg) and the mixture was stirred at 120°C for 3 hours Upon completion of the reaction, to the reaction mixture were added water and the mixture was stirred at room temperature for 30 minutes resulting solid substance was separated by filtration, washed with diisopropyl ether and dried to obtain specified in the title compound (90 mg) in the form yellow crystals.

1H-NMR (CDCl3) δ 2,7 (3H, c)3,98 (3H, c), of 8.04 (2H, d, J=8,4 Hz), 8,24 (2H, d, J=8,4 Hz), 8,63 (1H, c), 8,77 (1H, c).

(ii) Obtaining 4-[7-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]methylbenzoate

Specified in the title compound (135 mg) was obtained as a pale yellow solid interaction by the similar method of example 97 using 4-[7-(methylthio)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]methylbenzoate (115 mg), 3-methyl-4-[(6-methylpyridin-3-yl)oxy]aniline (82 mg) and pyridine hydrochloride (66 mg).

1H-NMR (CDCl3) δ 2,32 (3H, c), of 2.54 (3H, c)to 3.99 (3H, c), to 6.95 (1H, d, J=8.7 Hz), 7,10 for 7.12 (2H, m), 7,73 (1H, DD, J=2.7, and 8.7 Hz), 7,81-of 7.82 (2H, m), of 8.00 (2H, d, J=8,4 Hz), compared to 8.26 (2H, d, J=8,4 Hz), of 8.27 (1H, c), 8,55 (1H, c), 8,56 (1H, c).

Example 116

Getting 4-[7-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]benzoic acid

Specified in the title compound (91 mg) was obtained as white crystals by the interaction is similar to the method of example 101, using 4-[7-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]methylbenzoate (110 mg) and 1H. an aqueous solution of sodium hydroxide (0.4 ml).

1H-NMR (DMSO-d6) δ of 2.21 (3H, c), is 2.44 (3H, c), 6,98 (1H, d, J=9.0 Hz), 7,21-7,26 (2H, m), of 7.90 (1H, DD, J=2.7, and 8.7 Hz), 8,03 (1H, m), 8,12 were 8.22 (6H, m), scored 8.38 (1H, c), of 9.30 (1H, c), and 10.3 (1H, user. c).

Example 117

Obtaining N-(2-methoxyethyl)-4-[7-({3-IU the Il-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]benzamide

Specified in the title compound (63 mg) was obtained as white crystals by the interaction is similar to the method of example 106 using 4-[7-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]benzoic acid (75 mg), 2-methoxyethylamine (17 mg), 1-hydroxybenzotriazole (34 mg), hydrochloride of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (48 mg) and triethylamine (0,14 ml).

1H-NMR (CDCl3) δ 2,31 (3H, c), of 2.54 (3H, c), of 3.43 (3H, c), 3,60-3,63 (2H, m), 3,69-3,74 (2H, m), is 6.61 (1H, user. c)of 6.96 (1H, d, J=8.7 Hz), 7,10 for 7.12 (2H, m), 7,72 (1H, DD, J=2,4, and 8.4 Hz), 7,81 (1H, t, J=3.3 Hz), 8,00 (4H, c), of 8.27 (1H, m), 8,53 (1H, c), 8,55 (1H, c).

Example 118

Obtain {4-[7-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]phenyl}methanol

(i) Obtaining 4-[7-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]benzaldehyde

Specified in the title compound (60 mg) was obtained as pale-yellow crystals by the interaction is similar to the method of example 115 (i), using N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-1H-pyrazolo[4,3-d]pyrimidine-7-amine (100 mg) and 4-forventelige (37 mg).

1H-NMR (DMSO-d6) δ of 5.26 (2H, c), 7,16-to 7.35 (4H, m), 7,46 (1H, m), to 7.93 (1H, DD, J=2,6, 8,8 Hz), 8,18 (2H, d, J=8,4 Hz), 8,30 (1H, d, J=2.2 Hz), scored 8.38-8,43 (3H, m), 9,40 (1H, c), a 10.1 (1H, c), and 10.3 (1H, c).

(ii) Obtain {4-[7-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl] - dryer is l}methanol

To a solution of 4-[7-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]benzaldehyde (50 mg) in methanol (2 ml) was added sodium borohydride (2 mg) under ice cooling and the mixture was stirred for 30 minutes At the end of the reaction, the reaction solution was concentrated under reduced pressure and the residue was subjected to chromatography on a column of silica gel (tetrahydrofuran/ethyl acetate=1/1) to obtain specified in the connection header (20 mg) as a white solid.

1H-NMR (DMSO-d6) δ 4,60 (2H, d, J=5.8 Hz), a 5.25 (2H, c), 5,38 (1H, t, J=5.8 Hz), 7,16-to 7.35 (3H, m), 7,49 (1H, m), 7,56 (2H, d, J=8,8 Hz), to 7.93 (1H, m), of 8.09 (2H, d, J=8,8 Hz), 8,30 (1H, d, J=2.4 Hz), scored 8.38 (1H, c), which 9.22 (1H, c), 10,2 (1H, c).

Example 119

Obtain N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-2-[4-({[2-(methylsulphonyl)ethyl]amino}methyl)phenyl]-2H-pyrazolo[4,3-d]pyrimidine-7-amine

To a solution of 4-[7-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]benzaldehyde (80 mg), and hydrochloride of 2-(methylsulphonyl) - ethylamine (40 mg) in N,N-dimethylformamide (2 ml) was added acetic acid (0,02 ml) and the mixture was stirred at room temperature for 1 h and Then added triacetoxyborohydride sodium (54 mg) and the mixture was stirred at the same the temperature for 2 hours after the reaction was added saturated aqueous sodium hydrogen carbonate solution and the mixture koncentrirane and under reduced pressure. The residue was extracted with ethyl acetate, the organic layer was washed with water and saturated salt solution and concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel (ethyl acetate/methanol=5/1) to obtain the specified title compound (70 mg) as a white solid.

1H-NMR (CDCl3) δ to 3.02 (3H, c), up 3.22 (4H, c)to 3.92 (2H, c)to 5.17 (2H, c), 6,98? 7.04 baby mortality (2H, m), 7,21-7,26 (3H, m), of 7.36 (1H, m), 7,52 (2H, d, J=8.1 Hz), 7.68 per-7,71 (2H, m), to 7.84 (2H, d, J=8.1 Hz), with 8.05 (1H, d, J=2.4 Hz), to 8.45 (1H, c), 8,54 (1H, c).

Example 120

Getting 2-({4-[7-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]benzyl}amino)ethanol

Specified in the title compound (83 mg) was obtained as pale-yellow crystals by the interaction is similar to the method of example 119, using 4-[7-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]benzaldehyde (120 mg), ethanolamine (23 mg) and triacetoxyborohydride sodium (134 mg).

1H-NMR (DMSO-d6) δ at 2.59 (2H, t, J=6.0 Hz), 3,48 (2H, m), 3,80 (2H, c), 4,51 (1H, user. c)a 5.25 (2H, c), 7,16-7,34 (5H, m), 7,46 (1H, m), EUR 7.57 (2H, d, J=7.8 Hz), to $ 7.91 (1H, DD, J=1,8, 9.0 Hz), 8,07 (2H, d, J=7.8 Hz), 8,30 (1H, d, J=1,8 Hz), scored 8.38 (1H, c), of 9.21 (1H, c), 10,2 (1H, c).

Example 121

Obtain N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-2-(4-{[(2-morpholine-4-retil)amino]methyl}phenyl)-2H-pyrazolo[4,3-d]pyrimidine-7-amine

The decree of the TES in the title compound (68 mg) was obtained as pale-yellow crystals by the interaction is similar to the method of example 119, using 4-[7-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]benzaldehyde (80 mg), N-(2-amino-ethyl)research (33 mg) and triacetoxyborohydride sodium (54 mg).

1H-NMR (CDCl3) δ is 2.44 (4H, t, J=4.5 Hz), 2,53 (2H, t, J=6.0 Hz), is 2.74 (2H, t, J=6.0 Hz), 3,70 (4H, t, J=4.5 Hz), 3,91 (2H, c), 5,16 (2H, c), 6,98 (1H, d, J=8.7 Hz), 7,02 (1H, m), 7,19-of 7.25 (3H, m), 7,35 (1H, m), 7,52 (2H, d, J=8.7 Hz), to 7.67-7,71 (2H, m), 7,82 (2H, d, J=8.7 Hz), of 8.04 (1H, d, J=2.4 Hz), 8,43 (1H, c), charged 8.52 (1H, c).

Example 122

Getting 2-[7-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-1H-pyrazolo[4,3-d]pyrimidine-1-yl]ethanol

2-[7-({3-Chloro-4-[(3-terbisil)oxy]phenyl}amino)-1H-pyrazolo[4,3-d]pyrimidine-1-yl]ethylbenzoic received in the form of a mixture with 1-methyl-2-pyrrolidone interaction similar to the method of example 97, using 2-[7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidine-1-yl]ethylbenzoic (130 mg), 3-chloro-4-[(3-terbisil)oxy]aniline (104 mg) and pyridine hydrochloride (72 mg).

Specified in the title compound (60 mg) was obtained as a pale yellow solid interaction by the similar method of example 101, using the above mixture and 1H. an aqueous solution of sodium hydroxide (0.2 ml).

1H-NMR (DMSO-d6) δ a 3.87-3,93 (2H, m), and 4.75 (2H, t, J=5.7 Hz), 5,24 (2H,c), 6,27 (1H, t, J=3,9 Hz), 7,13-to 7.32 (4H, m), of 7.48 (1H, m), 7,55 (1H, DD, J=2,4, and 9.3 Hz), 7,86 (1H, d, J=1,8 Hz), 8,17 (1H, c), at 8.36 (1H, c), 9,85 (1H, c).

Example 123

Getting 2-[7-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]ethanol

2-[7-({3-Chloro-4-[(3-terbisil)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]ethylbenzoic received in the form of a mixture with 1-methyl-2-pyrrolidone interaction similar to the method of example 97, using 2-[7-(methylthio)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]ethylbenzoic (120 mg), 3-chloro-4-[(3-terbisil)oxy]aniline (96 mg) and pyridine hydrochloride (66 mg).

Specified in the title compound (86 mg) was obtained as a pale yellow solid interaction by the similar method of example 101, using the above mixture and 1H. an aqueous solution of sodium hydroxide (0.2 ml).

1H-NMR (DMSO-d6) δ 3,88-3,93 (2H, m), 4,50 (2H, t, J=5.4 Hz), 5,04 (1H, t, J=5.7 Hz), 5,23 (2H, c), 7,14-to 7.32 (4H, m), 7,46 (1H, m), 7,88 (1H, DD, J=2.7, and 9.0 Hz), of 8.28 (1H, d, J=1,8 Hz), 8,31 (1H, c), to 8.45 (1H, c), 10,12 (1H, c).

Example 124

Getting 2-[7-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-1H-pyrazolo[4,3-d]pyrimidine-1-yl]ethanol

2-[7-({3-Methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-1H-pyrazolo[4,3-d]pyrimidine-1-yl]ethylbenzoic received in the form of a mixture with 1-methyl-2-pyrrolidone interaction similar to the method of example 101, using 2-[7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidine-1-yl]ethylbenzoic (190 mg), 3-methyl-4-[(6-methylpyridin-3-yl)oxy]aniline (129 mg) and pyridine hydrochloride (10 mg).

Specified in the title compound (88 mg) was obtained as a pale yellow solid interaction by the similar method of example 101, using the above mixture and 1H. an aqueous solution of sodium hydroxide (0.3 ml).

1H-NMR (CDCl3) δ 2,22 (3H, c), 2,48 (3H, c), 4,25 (2H, user. c)was 4.76 (2H, user. c)6,01 (1H, user. c)6,86 (1H, d, J=8.7 Hz), was 7.08 (1H, d, J=8.7 Hz), 7,16 (1H, DD, J=3,0, to 8.7 Hz), was 7.45 (1H, DD, J=2.7, and 8.7 Hz), 7,56 (1H, d, J=2.7 Hz), with 8.05 (1H, d, J=3.0 Hz), of 8.37 (1H, c), 9,88 (1H, c).

Example 125

Getting 2-[7-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]ethanol

2-[7-({3-Methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]ethylbenzoic received in the form of a mixture with 1-methyl-2-pyrrolidone interaction similar to the method of example 97, using 2-[7-(methylthio)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]ethylbenzoic (115 mg), 3-methyl-4-[(6-methylpyridin-3-yl)oxy]aniline (78 mg) and pyridine hydrochloride (63 mg).

Specified in the title compound (95 mg) was obtained as a pale yellow solid interaction by the similar method of example 101, using the above mixture and 1H. an aqueous solution of sodium hydroxide (0.3 ml).

1H-NMR (CDCl3) δ of 2.24 (3H, c), 2,52 (3H, c)to 4.16 (2H, t, J=4.5 Hz), 4.26 deaths (1H, user. c), 4,50-a 4.53 (2H, m)6,86 (1H, d, J=8.7 Hz), 7,05 for 7.12 (2H, m), EUR 7.57-to 7.61 (2H, m), of 7.69 (1H, d, J=2.7 Hz), of 7.97 (1H, c), 8,23 (1H, m), 8.34 per 1H, c).

Example 126

Obtain 3-[7-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-1H-pyrazolo[4,3-d]pyrimidine-1-yl]propanol

Specified in the title compound (240 mg) was obtained as a pale yellow solid interaction by the similar method of example 122, and using 3-[7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidine-1-yl]propylbenzoate (623 mg), 3-chloro-4-[(3-terbisil)oxy]aniline (477 mg) and pyridine hydrochloride (329 mg) and 1H. an aqueous solution of sodium hydroxide (0.5 ml).

1H-NMR (DMSO-d6) δ 1,97-2,04 (2H, m), 3.25 to or 3.28 (2H, m), 4,71(2H, t, J=6.6 Hz), 5,27 (2H, c), 5,44 (1H, t, J=4,8 Hz), 7,16-7,34 (4H, m), of 7.48 (1H, m), EUR 7.57 (1H, DD, J=2.7, and 9.0 Hz), 7,82 (1H, d, J=2.4 Hz), 8,19 (1H, c), 8,35 (1H, c), which 9.22 (1H, c).

Example 127

Obtain 3-[7-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]propanol

Specified in the title compound (512 mg) was obtained as a pale yellow solid interaction by the similar method of example 123, using 3-[7-(methylthio)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]propylbenzoate (556 mg), 3-chloro-4-[(3-terbisil)oxy]aniline (426 mg), pyridine hydrochloride (293 mg) and 1H. an aqueous solution of sodium hydroxide (10 ml).

1H-NMR (DMSO-d6) δ 2.06 to a 2.13 (2H, m), 3,41-of 3.46 (2H, m), a 4.53 (2H, t, J=6.9 Hz), 4,70 (1H, t, J=5.4 Hz), 5,24 (2H, c), 7,16-7,33 (4H, m), 7,46 (1H, m), 7,89 (1H, DD, J=2,4, and 9.0 Hz), of 8.28 (1H, d, J=2.4 Hz), 8,32 (1H, c), 8,51 (1H, c), 0,12 (1H, c).

Example 128

Getting 4-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5,6-dihydro-4H-pyrazolo[4.5.1-de]pteridine

A solution of 2-[7-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-1H-pyrazolo[4,3-d]pyrimidine-1-yl]ethanol (40 mg), 1,1'-(azodicarbon)piperidine (48 mg) and tributylphosphine (40 mg) in tetrahydrofuran (2 ml) was stirred at room temperature for 15 hours At the end of the reaction, to the reaction mixture was added water, the mixture was diluted with ethyl acetate and washed with saturated solution of salt. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (hexane/ethyl acetate=4/1→1/4) to obtain the specified title compound (31 mg) as a white solid.

1H-NMR (CDCl3) δ 4,32 (2H, DD, J=5.0 and 6.6 Hz), to 4.62 (2H, DD, J=5.0 and 6.6 Hz), 5,19 (2H, c),? 7.04 baby mortality (1H, d, J=9,2 Hz), 7,05 (1H, m), 7.18 in-7,26 (2H, m), 7,32-the 7.43 (2H, m), 7,55 (1H, d, J=2.6 Hz), of 8.09 (1H, c), 8,51 (1H, c).

Example 129

Getting 4-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}-5,6-dihydro-4H-pyrazolo[4.5.1-de]pteridine

Specified in the title compound (21 mg) was obtained as a pale yellow solid interaction by the similar method of example 128, using 2-[7-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)-1H-pyrazolo[4,3-d]pyrim the DIN-1-yl]ethanol (30 mg), 1,1'-(azodicarbon)piperidine (40 mg) and tributylphosphine (32 mg).

1H-NMR (CDCl3) δ of 2.34 (3H, c), to 2.55 (3H, c), 4,36 (2H, t, J=5.7 Hz), with 4.64 (2H, t, J=5.7 Hz), 6,92 (1H, d, J=8,4 Hz), 7,13 (1H, d, J=8,4 Hz), 7,20 (1H, DD, J=2.7, and an 8.4 Hz), 7,27 (1H, DD, J=2,4, and 8.4 Hz), 7,41 (1H, d, J=the 2.4 Hz), of 8.09 (1H, c), 8,30 (1H, d, J=2.7 Hz), 8,53 (1H, c).

Example 130

Obtain 6-{3-chloro-4-[(3-terbisil)oxy]phenyl}-6,7,8,9-tetrahydro-1,3,5,6,9a-pentosanase[cd]azulene

Specified in the title compound (29 mg) was obtained as a pale yellow solid interaction by the similar method of example 128, using 3-[7-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-1H-pyrazolo[4,3-d]pyrimidine-1-yl]propanol (60 mg), 1,1'-(azodicarbon)piperidine (70 mg) and tributylphosphine (57 mg).

1H-NMR (CDCl3) δ 2,49-of 2.56 (2H, m), a 4.03 (2H, m), to 4.62 (2H, t, J=5.7 Hz), 5,19 (2H, c), 7,02 (1H, d, J=8.7 Hz), 7,05 (1H, m), to 7.15 (1H, DD, J=2.7, and 9.0 Hz), 7,21-7,26 (2H, m), 7,35-7,42 (2H, m)to 8.12 (1H, c), of 8.37 (1H, c).

Example 131

Obtain N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-2-(3-{[2-(methylsulphonyl)ethyl]amino}propyl)-2H-pyrazolo[4,3-d]pyrimidine-7-amine

A solution of 3-[7-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]propanol (50 mg), N-[2-(methylsulphonyl)ethyl]-2-nitrobenzenesulfonamide (47 mg), 1,1'-(azodicarbon)dipiperidino (59 mg) and tributylphosphine (47 mg) in tetrahydrofuran (2 ml) was stirred at room temperature over 4 hours Upon completion of the reaction, to the reaction mixture was added water, the mixture was diluted with ethyl acetate and washed with saturated solution of salt. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (ethyl acetate/methanol=4/1→1/4) to obtain N-{3-[7-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]propyl}-N-[2-(methylsulphonyl)ethyl]-2-nitrobenzenesulfonamide. To a solution of the obtained compound in tetrahydrofuran (2 ml) was added 2-mercaptoethanol (12 mg) and 1,8-diazabicyclo[5.4.0]undec-7-ene (23 mg) and the mixture was stirred at room temperature for 3 hours after the reaction, the reaction mixture was concentrated under reduced pressure and the residue was purified by chromatography on a column of silica gel (ethyl acetate/methanol=10/1) to obtain the specified title compound (34 mg) as a white solid.

1H-NMR (CDCl3) δ 2,05 with 2.14 (2H, m), to 2.57 (2H, t, J=6.3 Hz), is 3.08 (3H, c), 3,14-and 3.16 (2H, m), 3,22-3,26 (2H, m), of 4.54 (2H, t, J=6.3 Hz), 5,16 (2H, c), 6,97 (1H, d, J=8.7 Hz), 7,02 (1H, m), 7,20-7,26 (3H, m), of 7.36 (1H, dt, J=6,3, and 7.8 Hz), 7,71 (1H, DD, J=2.7, and 9.0 Hz), to 7.99 (2H, c), of 8.09 (1H, d, J=2.7 Hz), 8,49 (1H, c).

Example 132

Obtain N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-2-{3-[(2-morpholine-4-retil)amino]propyl}-2H-pyrazolo[4,3-d]pyrimidine-7-amine

Specified in the header is the compound (32 mg) was obtained as a pale yellow solid interaction by the similar method of example 131, using 3-[7-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]propanol (60 mg), N-(2-morpholine-4-retil)-2-nitrobenzenesulfonamide (53 mg), 1,1'-(azodicarbon)dipiperidino (71 mg), tributylphosphine (57 mg), 2-mercaptoethanol (12 mg) and 1,8-diazabicyclo[5.4.0]undec-7-ene (23 mg).

1H-NMR (CDCl3) δ 2,42 is 2.51 (8H, m), 2,59-of 2.72 (4H, m), 3,70 (4H, t, J=4,8 Hz), 4,51 (2H, t, J=6.8 Hz), 5,15 (2H, c), 6,97 (1H, d, J=8,8 Hz), 7,02 (1H, m), 7,19-7,26 (2H, m), 7,31-7,42 (2H, m), 7,66 (2H, m), 7,98 (1H, c), 8,01 (1H, d, J=2,8 Hz), 8,49 (1H, c).

Example 133

Obtain N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-2-{3-[(2-methoxyethyl)amino]propyl}-2H-pyrazolo[4,3-d]pyrimidine-7-amine

Specified in the title compound (26 mg) was obtained as a pale yellow solid interaction by the similar method of example 131, using 3-[7-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidine-2-yl]propanol (60 mg), N-(2-methoxyethyl)-2-nitrobenzenesulfonamide (44 mg), 1,1'-(azodicarbon)dipiperidino (71 mg), tributylphosphine (57 mg), 2-mercaptoethanol (12 mg) and 1,8-diazabicyclo[5.4.0]undec-7-ene (23 mg).

1H-NMR (CDCl3) δ 2,14-to 2.18 (2H, m), 2,61 (2H, t, J=6.6 Hz), was 2.76 (2H, t, J=5,1 Hz), 3,37 (3H, c), a 3.50 (2H, t, J=5,1 Hz)to 4.52 (2H, t, J=6.6 Hz), 5,15 (2H, c), 6,97 (1H, d, J=9.0 Hz), 7,01 (1H, m), 7.18 in-7,26 (4H, m), to 7.35 (1H, m), 7,58 (1H, user. c), the 7.65 (1H, DD, J=2,4, and 8.7 Hz), 7,99-of 8.00 (2H, m), 8,48 (1H, c).

Example 134

Getting 2-{[2-the ENT-4-(1H-pyrazolo[4,3-d]pyrimidine-7-ylamino)phenoxy]methyl}benzonitrile

Specified in the title compound (96 mg) was obtained as a pale yellow solid interaction by the similar method of example 97 using 7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidine (80 mg), 2-[(4-amino-2-chlorophenoxy)methyl]benzonitrile (125 mg) and pyridine hydrochloride (83 mg).

1H-NMR (DMSO-d6) δ of 2.23 (3H, c), of 5.26 (2H, c), to 7.09 (1H, d, J=8.7 Hz), 7,54-to 7.77 (5H, m), 7,92 (1H, d, J=8.7 Hz), to 8.20 (1H, user. c)to 8.34 (1H, user. c)to 9.45 (1H, user. c)to 12.8 (1H, user. c).

Example 135

Getting 2-{[2-methyl-4-(1H-pyrazolo[4,3-d]pyrimidine-7-ylamino)phenoxy]methyl}benzonitrile

Specified in the title compound (110 mg) was obtained as a pale yellow solid interaction by the similar method of example 97 using 7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidine (80 mg), 2-[(4-amino-2-methylphenoxy)methyl]benzonitrile (115 mg) and pyridine hydrochloride (83 mg).

1H-NMR (DMSO-d6) δ of 2.23 (3H, c), of 5.26 (2H, c), to 7.09 (1H, d, J=8.7 Hz), 7,54-to 7.77 (5H, m), 7,92 (1H, d, J=8.7 Hz), to 8.20 (1H, user. c)to 8.34 (1H, user. c)to 9.45 (1H, user. c)to 12.8 (1H, user. c).

Example 136

Obtain 3-[2-chloro-4-(1H-pyrazolo[4,3-d]pyrimidine-7-ylamino)phenoxy]benzonitrile

Specified in the title compound (89 mg) was obtained as a pale yellow solid interaction by the similar method of example 97 using 7-(methylthio)-1H-pyrazolo[4,3-d]is rimidine (80 mg), 3-(4-amino-2-chlorophenoxy)benzonitrile (117 mg) and pyridine hydrochloride (83 mg).

1H-NMR (DMSO-d6) δ 7,26-to 7.35 (2H, m), 7,46 (1H, m), 7,55-to 7.59 (2H, m), 7,89 (1H, m), 8,39 (1H, user. c)8,46 (2H, c), 10,16 (1H, user. c), and 12.6 (1H, user. c).

Example 137

Obtain 3-[2-methyl-4-(1H-pyrazolo[4,3-d]pyrimidine-7-ylamino)phenoxy]benzonitrile

Specified in the title compound (98 mg) was obtained as a pale yellow solid interaction by the similar method of example 97 using 7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidine (80 mg), 3-(4-amino-2-methylphenoxy)benzonitrile (108 mg) and pyridine hydrochloride (83 mg).

1H-NMR (DMSO-d6) δ to 2.18 (3H, c), to 7.09 (1H, d, J=8.7 Hz), 7,24 (1H, m), 7,37 (1H, m), 7,53-to 7.59 (2H, m), 7,86 (1H, d, J=8.7 Hz), to 7.93 (1H, user. c), 8,32 (1H, user. c)8,42 (1H, user. c)9,85 (1H, user. c), and 12.2 (1H, user. c).

Example 138

Getting 2-{2-[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethoxy}ethanol

(i) Obtaining 2-[2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethoxy]ethylbenzoic

To a solution of 2,2'-oxydiethanol (2,12 g) in pyridine (20 ml) was added benzoic anhydride (4.52 g) in small portions under ice cooling and the reaction mixture was stirred, allowing to warm to room temperature for 18 hours, the Pyridine is evaporated under reduced pressure and the obtained residue was diluted with diethyl ether (20 ml) was Added 5% aqueous sodium hydrogen carbonate solution (100 ml) and the mixture was extracted with diethyl ether (100 ml×3). The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on silica gel (eluent: hexane/ethyl acetate=95/5→40/60). The target fraction was concentrated under reduced pressure and dried to obtain 2-(2-hydroxyethoxy)ethylbenzoic (of 2.21 g). To a solution of the obtained 2-(2-hydroxyethoxy)ethylbenzoic (2.10 g) in dichloromethane (10 ml) was added 1-iterranean-2,5-dione (2.70 g) and triphenylphosphine (3,14 g) in small portions under ice cooling and the mixture was stirred for 14 h, the Reaction mixture was poured into 5% aqueous sodium hydrogen carbonate solution (100 ml) and was extracted with ethyl acetate (120 ml×3). The organic layer was washed successively with water and saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on silica gel (eluent: hexane/ethyl acetate=100/0→60/40). The target fraction was concentrated under reduced pressure and dried to obtain 2-(2-iodoxy)ethylbenzoic (2,05 g) as a colorless transparent oil.

To a suspension of 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (0,659 g) in N,N-dimethylformamide (5.0 ml) was added cesium carbonate (3.13 g) under ice cooling and the reaction mixture was stirred, allowing to warm to room temperature over 15 minutes To the reaction mixture was added 2-(2-iodoxy)ethylbenzoic (1.45 g)obtained is earlier, and the mixture was stirred at room temperature for 15 hours, the Reaction mixture was poured into 5% aqueous sodium hydrogen carbonate solution (100 ml) and was extracted with ethyl acetate (150 ml×3). The organic layer was washed successively with water and saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on silica gel (eluent: hexane/ethyl acetate=95/5→60/40). The target fraction was concentrated under reduced pressure and dried to obtain specified in the connection header (0,822 g) as a colorless transparent oil.

1H-NMR (CDCl3) δ RUB 3,718 (2H, dt, J=3.0 a, and 6.6 Hz), 3,887 (2H, t, J=5,1 Hz)4,412 (2H, dt, J=3.0 a, and 6.6 Hz), 4,680 (2H, t, J=5,1 Hz)6,566 (1H, d, J=3.3 Hz), 7,404-7,462 (2H, m), 7,542-7,600 (2H, m), 7,944-7,982 (2H, m)8,665 (1H, c).

(ii) Obtain 2-{2-[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethoxy}ethylbenzoic

To a solution of 2-[2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethoxy]ethylbenzoic (802 mg) in 1-methyl-2-pyrrolidone (8.0 ml) was added 3-chloro-4-[(3-terbisil)oxy]aniline (745 mg) and the mixture was stirred on an oil bath at 100°C for 2 h the Reaction mixture was allowed to cool to room temperature, diluted with 5% aqueous sodium hydrogen carbonate solution (25 ml) and was extracted with mixed solvent (50 ml×3) ethyl acetate-tetrahydrofuran (3/1). The solvent is perivale under reduced pressure and the obtained residue was subjected to chromatography on basic silica gel (eluent: hexane/ethyl acetate=95/5→0/100). The target fraction was concentrated under reduced pressure and dried to obtain specified in the connection header (1141 mg) as a yellow amorphous solid.

1H-NMR (CDCl3) δ 3,901-3,931 (2H, m)4,036 (2H, t, J=4, 2 Hz), 4,452-4,483 (2H, m)4,540 (2H, t, J=4,2 Hz)5,033 (2H, c), 6,590 (1H, d, J=3.0 Hz), 6,704 (1H, d, J=9.0 Hz), 7,005 (1H, TD, J=1,8, 7.5 Hz), 7,164-7,372 (7H, m)7,511 (1H, TT, J=1,8, 7.5 Hz), 7,679 (1H, d, J=3.0 Hz), 7,769 (1H, t, J=1,8 Hz), 7,788 (1H, t, J=0.6 Hz), 8,431 (1H, c)8,511 (1H, c).

(iii) Obtain 2-{2-[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethoxy}ethanol

To a solution of 2-{2-[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethoxy}etilbenzene (760 mg) in tetrahydrofuran (7.0 ml) was added 1N. an aqueous solution of sodium hydroxide (7.0 ml) and the mixture was stirred at room temperature for 14 hours was Added to the reaction mixture 1H. hydrochloric acid (7.0 ml), the mixture was stirred at room temperature for 10 minutes and was extracted with a mixed solvent (100 ml×3) ethyl acetate-tetrahydrofuran (1/1). The organic layer was washed successively with 5% aqueous sodium hydrogen carbonate solution and saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column with a basic silica gel (eluent: ethyl acetate/methanol=100/0→90/10). Target fracc the Yu was concentrated under reduced pressure. A mixed solvent of ethanol-isopropyl ether (1/4) was added to the residue, the mixture was heated up to 80°C and then allowed to cool to room temperature. The precipitate was separated by filtration and dried under reduced pressure to obtain specified in the title compound (431 mg) as white powdery crystals.

1H-NMR (DMSO-d6) δ 3,471-3,478 (4H, m)3,817 (2H, t, J=4.6 Hz), 4,616 (2H, t, J=4.6 Hz), 4,681-4,712 (1H, m)5,234 (2H, c), 6,480 (1H, d, J=3.2 Hz), 7,173-7,212 (2H, m), 7,289-7,339 (2H, m), 7,433-7,523 (2H, m)7,641 (1H, d, J=3.2 Hz), 7,829 (1H, d, J=3.2 Hz), 8,271 (1H, c)8,698 (1H, c).

Melting point: 168-169°C.

Example 139

Getting 4-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]butane-1-ol

(i) Obtaining 4-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)butyl acetate

To a suspension of 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (0,768 g) in N,N-dimethylformamide (10 ml) was added cesium carbonate (2,01 g) under ice cooling and the reaction mixture was stirred, allowing to warm to room temperature over 15 minutes To the reaction mixture was added dropwise 4-bromobutyrate (1.26 g) and the mixture was stirred at room temperature for 30 hours, the Reaction mixture was poured into 5% aqueous sodium hydrogen carbonate solution (80 ml) and was extracted with ethyl acetate (100 ml×3). The organic layer was washed successively with water and saturated salt solution is dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on silica gel (eluent: hexane/ethyl acetate=95/5→0/100). The target fraction was concentrated under reduced pressure and dried to obtain specified in the connection header (1,084 g) as a colorless transparent oil.

1H-NMR (CDCl3) δ 1,636-1,730 (2H, m), 1,874-is 1.971 (2H, m), 2,047 (3H, c)4,098 (2H, t, J=6.3 Hz), 4,512 (2H, t, J=6.3 Hz), 6,718 (1H, d, J=3.3 Hz), 7,482 (1H, d, J=3.3 Hz), 8,690 (1H, c).

(ii) Obtaining 4-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]butyl acetate

To a solution of 4-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)butyl acetate (302 mg) in isopropyl alcohol (2,24 ml) was added 3-chloro-4-[3-(trifluoromethyl)phenoxy]aniline (421 mg) and the mixture was stirred on an oil bath at 100°C for 3.5 hours the Reaction mixture was allowed to cool to room temperature, was added 5% aqueous sodium hydrogen carbonate solution (35 ml) and the mixture was extracted with ethyl acetate (50 ml×3). The organic layer was washed successively with water and saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on basic silica gel (eluent: hexane/ethyl acetate=95/5→20/80). The target fraction was concentrated under reduced pressure and dried to obtain specified in the header with the unity (293 mg) as a white powder.

1H-NMR (CDCl3) δ 1,624-1,714 (2H, m), 1,924-2,005 (2H, m), 2,005 (3H, c), 4,108 (2H, t, J=6.0 Hz), 4,342 (2H, t, J=6.0 Hz), 6,573 (1H, d, J=3.3 Hz), 7,054 (1H, c), 7,083-7,471 (7H, m), 7,793 (1H, d, J=3.3 Hz), 8,526 (1H, c).

(iii) Obtaining 4-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]butane-1-ol

To a solution of 4-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]butyl acetate (281 mg) in tetrahydrofuran (4.0 ml) was added 1N. an aqueous solution of sodium hydroxide (2.8 ml) and the mixture was stirred at room temperature for 4.5 hours was Added 1N. an aqueous solution of hydrochloric acid (2.8 ml) and the mixture was stirred for 15 minutes, the Reaction mixture was poured into water (50 ml) and the mixture was extracted with ethyl acetate (50 ml×3). The organic layer was washed successively with 5% aqueous sodium hydrogen carbonate solution, water and saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on basic silica gel (eluent: hexane/ethyl acetate=95/5→0/100). The target fraction was concentrated under reduced pressure and dried. To the residue was added a mixture of ethanol-diisopropyl ether (5/95), and the mixture was stirred while heating to 80°C, allowed to cool to room temperature and gave an additional stand. The precipitate was separated by filtration. The precipitate is amywali diisopropyl ether and dried under reduced pressure to obtain specified in the title compound (214 mg) as white powdery crystals.

1H-NMR (DMSO-d6) δ 1,240-1,331 (2H, m), 1,690-1,782 (2H, m), 3,324-3,361 (2H, m)4,473 (1H, user. c)4,540 (2H, t, J=6.0 Hz), 6,492 (1H, d, J=3.0 Hz), 7,200-7,254 (2H, m)7,303 (1H, d, J=9.0 Hz), 7,472 (1H, d, J=9.0 Hz), 7,621 (1H, t, J=9.0 Hz), 7,653-7,713 (2H, m)7,970 (1H, c)8,351 (1H, c)8,632 (1H, c).

Example 140

Obtaining 3-(2-chloro-4-{[5-(2-hydroxyethyl)-5H-pyrrolo[3,2-d]pyrimidine-4-yl]amino}phenoxy)benzonitrile

(i) Obtaining 2-(4-{[3-chloro-4-(3-cianfrocca)phenyl]amino}-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethylbenzoic

To a suspension of 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (141 mg) in N,N-dimethylformamide (2.5 ml) was added cesium carbonate (358 mg) under ice cooling and the reaction mixture was stirred, allowing to warm to room temperature over 15 minutes To the reaction mixture were added 2-icatibant (298 mg) and the mixture was stirred at room temperature for 15 hours, the Reaction mixture was poured into 5% aqueous sodium hydrogen carbonate solution (50 ml) and was extracted with ethyl acetate (50 ml×3). The organic layer was washed successively with water and saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on silica gel (eluent: hexane/ethyl acetate=95/5→60/40). The target fraction was concentrated under reduced pressure and dried to obtain 2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethylbenzoic (205 mg) in VI is e a colorless transparent oil.

Specified in the title compound (311 mg) was obtained as yellow solid interaction similar to the method of example 42 (ii), using 3-(4-amino-2-chlorophenoxy)benzonitrile (211 mg) and a solution of 2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethylbenzoic (205 mg) in 1-methyl-2-pyrrolidone (1.3 ml).

1H-NMR (CDCl3) δ 4,693 (4H, c)6,688 (1H, d, J=3.0 Hz), 7,086-7,497 (8H, m), 7,609-7,727 (2H, m)7,962 (2H, d, J=6.9 Hz), 8,024 (2H, d, J=6.9 Hz), 8,569 (1H, c).

(ii) Obtaining 3-(2-chloro-4-{[5-(2-hydroxyethyl)-5H-pyrrolo[3,2-d]pyrimidine-4-yl]amino}phenoxy)benzonitrile

Specified in the title compound (187 mg) was obtained as pale yellow powder by the interaction is similar to the method of example 138 (iii)using 2-(4-{[3-chloro-4-(3-cianfrocca)phenyl]amino}-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethylbenzoic (310 mg).

1H-NMR (DMSO-d6) δ 3,977-3,990 (2H, m)4,542 (2H, user. c)6,470 (1H, d, J=3.0 Hz), 7,162-7,24 (3H, m), 7,421-7,625 (3H, m), 7,645 (1H, d, J=7,2 Hz), 7,989 (1H, d, J=3.0 Hz), 8,078 (1H, d, J=3.0 Hz), 8,368 (1H, c), 10,10 (1H, user. c).

Example 141

Obtain 3-[2-chloro-4-({5-[2-(2-hydroxyethoxy)ethyl]-5H-pyrrolo[3,2-d]pyrimidine-4-yl}amino)phenoxy]benzonitrile

(i) Obtaining 2-[2-(4-{[3-chloro-4-(3-cianfrocca)phenyl]amino}-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethoxy]ethylbenzoic

Specified in the title compound (117 mg) was obtained as a pale brown solid interaction similar is yodice example 138 (ii), using 2-[2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethoxy]ethylbenzoic (130 mg) and 3-(4-amino-2-chlorophenoxy)benzonitrile (112 mg).

1H-NMR (CDCl3) δ 4,051-4,077 (2H, m)4,206 (2H, t, J=4, 2 Hz), 4,582-4,599 (2H, m)4,610 (2H, t, J=4, 2 Hz), 6,781 (1H, d, J=3.0 Hz), 6,904 (1H, d, J=9.0 Hz), 7,195 (1H, TD, J=1,8, 7.5 Hz), 7,360-7,568 (7H, m)7,709 (1H, TT, J=1,8, 7.5 Hz), 7,872 (1H, d, J=3.0 Hz), 7,975 (1H, t, J=1,8 Hz), 7,968 (1H, t, J=0.6 Hz), 8,531 (1H, c)8,671 (1H, c).

(ii) Obtaining 3-[2-chloro-4-({5-[2-(2-hydroxyethoxy)ethyl]-5H-pyrrolo[3,2-d]pyrimidine-4-yl}amino)phenoxy]benzonitrile

Specified in the title compound (52 mg) was obtained as pale yellow powder by the interaction is similar to the method of example 138 (iii)using 2-[2-(4-{[3-chloro-4-(3-cianfrocca)phenyl]amino}-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethoxy]ethylbenzoic (92 mg).

1H-NMR (DMSO-d6) δ 3,578-3,693 (4H, m)3,617 (2H, t, J=4,8 Hz)4,515 (2H, t, J=4,8 Hz), 4,589-4,699 (1H, m)6,378 (1H, d, J=3.0 Hz), 7,153-7,181 (3H, m), 7,411-7,461 (1H, m), 7,553-7,663 (2H, m)7,840 (1H, d, J=3.2 Hz), 8,049 (1H, d, J=3.2 Hz), 8,377 (1H, c)8,879 (1H, c).

Example 142

Getting 2-[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]-N-(2-hydroxyethyl)ndimethylacetamide

(i) Obtain ethyl[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]acetate

To a solution of ethyl(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)acetate (530 mg) in isopropyl alcohol (4.0 ml) was added 3-chloro-4-[(3-terbisil)oxy]aniline (695 mg) and the mixture is stirred on an oil bath at 100°C for 2.5 hours The reaction mixture was allowed to cool to room temperature, diluted with 5% aqueous sodium hydrogen carbonate solution (25 ml) and was extracted with ethyl acetate (30 ml×3). The organic layer was washed successively with water and saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on basic silica gel (eluent: hexane/ethyl acetate=95/5→20/80). The target fraction was concentrated under reduced pressure and dried to obtain specified in the title compound (743 mg) as a white solid.

1H-NMR (CDCl3) δ 1,298-1,344 (3H, m), 4,338 (2H, q, J=7.2 Hz), 4,938 (2H, c), 5,132 (2H, c), 6,616 (1H, d, J=3,4 Hz)6,935 (1H, d, J=8,8 Hz), 6,979-7,056 (1H, m), 7,190-7,263 (3H, m), 7,301-7,426 (2H, m)7,638 (1H, t, J=2.4 Hz), 8,200 (1H, c), 8,499 (1H, user. c).

(ii) Obtaining [4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]acetic acid

Specified in the title compound (504 mg) was obtained as a pale-purple powder interaction, similar to the method of example 46, using ethyl[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]acetate (730 mg).

1H-NMR (DMSO-d6) δ 5,223 (2H, c)5,282 (2H, c), 6,480 (1H, d, J=3.0 Hz), 7,137-7,525 (7H, m)7,603 (1H, d, J=3.0 Hz), 7,666 (1H, d, J=3.0 Hz), 8,299 (1H, c).

(iii) Obtaining 2-[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimido the-5-yl]-N-(2-hydroxyethyl)ndimethylacetamide

Specified in the title compound (39 mg) was obtained as pale yellow powder by the interaction is similar to the method of example 36 using [4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]acetic acid (103 mg).

1H-NMR (DMSO-d6) δ of 3.23 (2H, m), of 3.46 (2H, m), 4,89 (1H, t, J=4.5 Hz), 5,04 (2H, c), with 5.22 (2H, c), 6,48 (1H, d, J=3.0 Hz), 7,14-7,24 (2H, m), 7,29-7,33 (2H, m), 7,43-7,53 (2H, m), 7,56 (1H, d, J=3.0 Hz), the 7.85 (1H, d, J=3.0 Hz), 8,29 (1H, c), 8,97 (1H, user. c)10,08 (1H, user. c).

Example 143

Obtain 3-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]propan-1-ol

To a solution of 3-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)propan-1-ol (201 mg)synthesized in example 53 (ii)in isopropyl alcohol (2.5 ml) was added 3-chloro-4-[3-(trifluoromethyl)phenoxy]aniline (381 mg) and the mixture was stirred on an oil bath at a temperature of 100°C in a period of 2.0 hours the Reaction mixture was allowed to cool to room temperature, diluted with 5% aqueous sodium hydrogen carbonate solution (25 ml) and was extracted with ethyl acetate (30 ml×3). The organic layer was washed successively with water and saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on basic silica gel (eluent: hexane/ethyl acetate=95/5→20/80). The target fraction was concentrated is under reduced pressure and dried. To the residue was added a mixture of ethanol-diisopropyl ether (1/9), and the mixture was stirred while heating to 80°C, allowed to cool to room temperature and addition to stand still. The precipitate was separated by filtration. The precipitate washed with diisopropyl ether and dried under reduced pressure to obtain specified in the title compound (375 mg) as white powdery crystals.

1H-NMR (DMSO-d6) δ 1,953 (2H, t, J=5.7 Hz), 3,380 (2H, t, J=5.7 Hz), 4,545 (2H, t, J=6.6 Hz), 5,372 (1H, user. c)6,527 (1H, d, J=3.0 Hz), 7,198-7,327 (3H, m)7,470 (1H, d, J=7.5 Hz), 7,592-7,707 (3H, m)7,981 (1H, d, J=3.0 Hz), 8,354 (1H, c), 9,038 (1H, user. c).

Example 144

Obtain hydrochloride of 2-{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethoxy}ethylcarbamate

To a solution of 2-{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethoxy}ethanol (84 mg) in a mixed solvent (1.0 ml) toluene-dichloromethane (1/1) was added trichloroacetonitrile (22 μl) under ice cooling and the mixture was stirred for 3 hours To the reaction mixture were added methanol (0.2 ml) and potassium carbonate (71 mg) and the mixture was stirred at room temperature for 12 hours, the Reaction mixture was poured into 5% aqueous sodium hydrogen carbonate solution (25 ml) and was extracted with ethyl acetate (30 ml×3). The organic layer was washed sequentially in the water and a saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on basic silica gel (eluent: ethyl acetate/methanol=100/0→95/5). The target fraction was concentrated under reduced pressure and dried to obtain 2-{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethoxy}ethylcarbamate (83 mg) as a colorless transparent oil. To the resulting colorless oil was added 4n. an ethyl acetate solution of hydrochloric acid. After stirring at room temperature for 3 h, the precipitate was separated by filtration, washed with diisopropyl ether, ethyl acetate and ice water, and dried under reduced pressure at 60°C with obtaining specified in the title compound (57 mg) as a pale yellow powder.

1H-NMR (DMSO-d6) δ of 3.57 (2H, t, J=3.0 Hz), with 3.79 (2H, t, J=3.0 Hz), of 3.96 (2H, t, J=6.0 Hz), with 4.64 (2H, t, J=6.0 Hz), 6.48 in (2H, user. c)6,56 (1H, c), 7,15-of 7.23 (2H, m), 7,30-7,34 (2H, m), 7,41 (1H, DD, J=3,0, 9.0 Hz), 7,47 (1H, dt, J=6,0, 9.0 Hz), 7,63 (1H, d, J=3.0 Hz), 7,82 (1H, c), of 8.28 (1H, c), 8,56 (1H, c).

Example 145

Getting 2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethanol

A mixture of 2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethylbenzoic (302 mg), 3-chloro-4-[3-(trifluoromethyl)phenoxy]aniline (288 mg) and 1-methyl-2-pyrrolidone (3 ml) was stirred at 120°C for 2 is. To the reaction mixture were added water and saturated aqueous solution of sodium bicarbonate and the mixture was extracted with ethyl acetate. An ethyl acetate layer was washed successively with water and saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel (eluent: ethyl acetate:hexane=20:80→100:0). The target fraction was concentrated under reduced pressure. To the residue was added diethyl ether to provide crystallization, then added diisopropyl ether and the mixture was filtered to obtain a white powder (286 mg). To a solution of the obtained white powder (221 mg) in methanol (5 ml) was added 1N. an aqueous solution of sodium hydroxide (0.8 ml) and the mixture was stirred at room temperature for 2 hours To the reaction mixture were added water and the mixture was extracted with ethyl acetate. An ethyl acetate layer was washed with saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was added ethyl acetate and diisopropyl ether, and then the mixture was filtered to obtain specified in the title compound (160 mg) as a white powder.

1H-NMR (CDCl3) δ of 4.16 (2H, t, J=4.4 Hz), to 4.38 (2H, t, J=4.4 Hz), 6,12 (1H, d, J=3.2 Hz), 6,97 (1H, d, J=3.2 Hz), to 7.09 (1H, d, J=8,8 Hz), 7,10-7,17 (1H, m), 7,21 (1, c)to 7.32 (1H, d, J=7,7 Hz), the 7.43 (1H, t, J=8.0 Hz), 7,52 (1H, DD, J=8,8, and 2.6 Hz), to 7.84 (1H, d, J=2.6 Hz), 8,24 (1H, c), 9,59 (1H, user. c).

Example 146

Obtain 2-[2-(4-{[3-chloro-4-(3-chlorophenoxy)phenyl]amino}-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethoxy]ethanol

A mixture of 2-[2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethoxy]ethylbenzoic (346 mg), 3-chloro-4-(3-chlorophenoxy)aniline (280 mg) and 1-methyl-2-pyrrolidone (3 ml) was stirred at 120°C for 2 hours To the reaction mixture were added water and saturated aqueous solution of sodium bicarbonate and the mixture was extracted with ethyl acetate. An ethyl acetate layer was washed successively with water and saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel (eluent: ethyl acetate:hexane=30:70→100:0). The target fraction was concentrated under reduced pressure. To a solution of the residue (431 mg) in methanol (10 ml) was added 1N. an aqueous solution of sodium hydroxide (1 ml) and the mixture was stirred at room temperature for 4 hours To the reaction mixture were added water and the mixture was extracted with ethyl acetate. An ethyl acetate layer was washed with saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was led from a mixture of ethyl acetate-Dyatlov the second broadcast receiving specified in the title compound (312 mg) as a white powder.

1H-NMR (CDCl3) δ is 2.05 (1H, user. c), 3,71-a-3.84 (4H, m), a 4.03 (2H, t, J=4.5 Hz), of 4.57 (2H, t, J=4.5 Hz), is 6.61 (1H, d, J=3.0 Hz), 6,83-to 6.88 (1H, m), 6,92 (1H, t, J=2.2 Hz), 7,01-7,06 (1H, m), 7,06 (1H, d, J=8,9 Hz), 7,19-7,27 (2H, m), to 7.61 (1H, DD, J=8,9, and 2.6 Hz), 7,89 (1H, d, J=2.6 Hz), charged 8.52 (1H, c), 8,82 (1H, user. c).

Example 147

Getting 2-{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethoxy}ethanol

A mixture of 2-[2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethoxy]ethylbenzoic (1,037 g), 3-chloro-4-[3-(trifluoromethyl)phenoxy]aniline (863 mg) and 1-methyl-2-pyrrolidone (10 ml) was stirred at 120°C for 1.5 hours was Added to the reaction mixture water and a saturated aqueous solution of sodium bicarbonate and the mixture was extracted with ethyl acetate. An ethyl acetate layer was washed successively with water and saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel (eluent: ethyl acetate:hexane=50:50→100:0). The target fraction was concentrated under reduced pressure. To a solution of the residue (1,420 g) in methanol (30 ml) was added 1N. an aqueous solution of sodium hydroxide (3 ml) and the mixture was stirred at room temperature for 1 h the Reaction mixture was concentrated under reduced pressure, was added to the reaction mixture water and the mixture was extracted with ethyl acetate. Ethyl is attny layer was washed with saturated salt solution and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to chromatography on a column of silica gel (eluent: methanol:acetic acid ethyl ester=0:100→5:95). The target fraction was concentrated under reduced pressure. Precipitated precipitated crystals were separated by filtration and washed with diethyl ether. The crude crystals are recrystallized from a mixture of ethyl acetate-diisopropyl ether to obtain specified in the connection header (933 mg) as a white powder.

1H-NMR (CDCl3) δ of 1.94 (1H, user. c), 3,71-of 3.85 (4H, m), a 4.03 (2H, t, J=4.4 Hz), of 4.57 (2H, t, J=4.4 Hz), 6,63 (1H, d, J=3.2 Hz), 7,07 (1H, d, J=8,9 Hz), 7,08-7,14 (1H, m), 7,19 (1H, c), 7,22 (1H, d, J=3.2 Hz), 7,31 (1H, d, J=7,7 Hz), 7,42 (1H, t, J=8.0 Hz), 7,63 (1H, DD, J=8,9, and 2.6 Hz), to $ 7.91 (1H, d, J=2.6 Hz), charged 8.52 (1H, c), 8,83 (1H, user. c).

Melting point: 130-132°C.

Example 148

Getting 2-{2-[4-({3-chloro-4-[3-(triptoreline)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethoxy}ethanol

Specified in the title compound (293 mg) was obtained as a white powder interaction, similar to the method of example 146 using 2-[2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethoxy]ethylbenzoic (346 mg), 3-chloro-4-[3-(triptoreline)phenoxy]aniline (334 mg) and 1-methyl-2-pyrrolidone (3 ml).

1H-NMR (CDCl3) δ 1,95 (1H, user. c), 3,71-a-3.84 (4H, m), a 4.03 (2H, t, J=4.5 Hz), of 4.57 (2H, t, J=4.5 Hz), 6,62 (1H, d, J=3.2 Hz), 6,80-to 6.95 (3H, m), was 7.08 (1H, d, J=8,8 Hz), 7,21 (1H, d, J=3.2 Hz, 7,30 (1H, t, J=8,2 Hz), a 7.62 (1H, DD, J=8,8, and 2.6 Hz), of 7.90 (1H, d, J=2.6 Hz), charged 8.52 (1H, c), 8,82 (1H, user. c).

Example 149

Obtain 1-{3-[2-chloro-4-({5-[2-(2-hydroxyethoxy)ethyl]-5H-pyrrolo[3,2-d]pyrimidine-4-yl}amino)phenoxy]phenyl}of ethanone

Specified in the title compound (493 mg) was obtained as a white powder interaction, similar to the method of example 146 using 2-[2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethoxy]ethylbenzoic (692 mg), 1-[3-(4-amino-2-chlorophenoxy)phenyl]ethanone (576 mg) and 1-methyl-2-pyrrolidone (5 ml).

1H-NMR (CDCl3) δ of 1.97 (1H, user. c), 2,58 (3H, c), 3,71-a-3.84 (4H, m), a 4.03 (2H, t, J=4.4 Hz), 4,58 (2H, t, J=4.4 Hz), 6,63 (1H, d, J=3.2 Hz), 7,06 (1H, d, J=8,9 Hz), 7,15-7,20 (1H, m), 7,22 (1H, d, J=3.2 Hz), 7,41 (1H, t, J=7.9 Hz), of 7.48-7,51 (1H, m), to 7.61 (1H, DD, J=8,9, and 2.6 Hz), 7,62-to 7.67 (1H, m), of 7.90 (1H, d, J=2.6 Hz), charged 8.52 (1H, c), 8,80 (1H, user. c).

Example 150

Obtain 1-{3-[2-chloro-4-({5-[2-(2-hydroxyethoxy)ethyl]-5H-pyrrolo[3,2-d]pyrimidine-4-yl}amino)phenoxy]phenyl}ethanol

To a solution of 1-{3-[2-chloro-4-({5-[2-(2-hydroxyethoxy)ethyl]-5H-pyrrolo[3,2-d]pyrimidine-4-yl}amino)phenoxy]phenyl}of ethanone (233 mg) in methanol (5 ml) was added sodium borohydride (38 mg) and the mixture was stirred at room temperature for 2 hours was Added to the reaction mixture water and the mixture was extracted with ethyl acetate. An ethyl acetate layer was washed with saturated salt solution and dried over anhydrous magnesium sulfate. Dissolve the ü evaporated under reduced pressure and the obtained residue was led from a mixture of ethyl acetate-diethyl ether to obtain specified in the title compound (225 mg) as a white powder.

1H-NMR (CDCl3) δ 2,47 (3H, d, J=6.4 Hz), 3,67-of 3.77 (4H, m)4,00 (2H, t, J=4.4 Hz), 4,58 (2H, t, J=4.4 Hz), 4,84 (1H, q, J=6.4 Hz), 6,62 (1H, d, J=3.3 Hz), 6,85-of 6.90 (1H, m), of 6.96-7,00 (1H, m), 7,01-to 7.09 (2H, m), 7.24 to to 7.32 (2H, m), 7,52 (1H, DD, J=8,9, and 2.6 Hz), 7,86 (1H, d, J=2.6 Hz), to 8.45 (1H, c).

Example 151

Obtain 2-[2-(4-{[3-chloro-4-(pyrimidine-5-yloxy)phenyl]amino}-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethoxy]ethanol

Specified in the title compound (63 mg) was obtained as a white powder interaction, similar to the method of example 146 using 2-[2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethoxy]ethylbenzoic (346 mg), 3-chloro-4-(pyrimidine-5-yloxy)aniline (360 mg) and 1-methyl-2-pyrrolidone (3 ml).

1H-NMR (CDCl3) δ of 2.08 (1H, user. c), and 3.72-a-3.84 (4H, m), a 4.03 (2H, t, J=4.4 Hz), 4,58 (2H, t, J=4.4 Hz), 6,63 (1H, d, J=3.1 Hz), 7,12 (1H, d, J=8.7 Hz), 7.23 percent (1H, d, J=3.1 Hz), to 7.67 (1H, DD, J=8,7, and 2.6 Hz), 7,95 (1H, d, J=2.6 Hz), 8,43 (2H, c), charged 8.52 (1H, c), 8,89 (1H, user. c)to 8.94 (1H, c).

Example 152

Obtaining 2-(2-{4-[(3-chloro-4-{[2-(trifluoromethyl)benzyl]oxy}phenyl)amino]-5H-pyrrolo[3,2-d]pyrimidine-5-yl}ethoxy)ethanol

Specified in the title compound (276 mg) was obtained as a white powder interaction, similar to the method of example 146 using 2-[2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethoxy]ethylbenzoic (277 mg), 3-chloro-4-{[2-(trifluoromethyl)benzyl]oxy}aniline (241 mg) and 1-methyl-2-pyrrolidone (3 ml).

1H-NMR (CDCl3) δ 2,02 (1H, in the Il. c), 3,68-3,81 (4H, m)4,00 (2H, t, J=4.4 Hz), a 4.53 (2H, t, J=4.4 Hz), of 5.34 (2H, c), to 6.58 (1H, d, J=3.2 Hz), 6,93 (1H, d, J=8,8 Hz), 7,17 (1H, d, J=3.2 Hz), 7,42 (1H, t, J=7,7 Hz), 7,49 (1H, DD, J=8,8 to 2.6 Hz), 7,60 (1H, t, J=7,7 Hz), 7,69 (1H, d, J=7,7 Hz), 7,76 (1H, d, J=2.6 Hz), 7,89 (1H, d, J=7,7 Hz), 8,46 (1H, c), to 8.57 (1H, user. c).

Example 153

Obtaining 2-(2-{4-[(3-chloro-4-{[3-(trifluoromethyl)benzyl]oxy}phenyl)amino]-5H-pyrrolo[3,2-d]pyrimidine-5-yl}ethoxy)ethanol

Specified in the title compound (393 mg) was obtained as a white powder interaction, similar to the method of example 146 using 2-[2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethoxy]ethylbenzoic (346 mg), 3-chloro-4-{[3-(trifluoromethyl)benzyl]oxy}aniline (302 mg) and 1-methyl-2-pyrrolidone (3 ml).

1H-NMR (CDCl3) δ 2,03 (1H, user. c), 3,68-of 3.80 (4H, m)4,00 (2H, t, J=4.4 Hz), of 4.54 (2H, t, J=4.4 Hz), to 5.17 (2H, c), 6,59 (1H, d, J=3.1 Hz), to 6.95 (1H, d, J=8,8 Hz), 7,17 (1H, d, J=3.1 Hz), of 7.48 to 7.62 (3H, m), 7,66-7,76 (3H, m), 8,46 (1H c), 8,58 (1H, user. c).

Example 154

Getting 5-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]pentane-1-ol

(i) Obtaining 5-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)pistillata

A mixture of 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (0.50 g), 5-bromopentanoate (0,71 ml), cesium carbonate (1,59 g) and N,N-dimethylformamide (5.0 ml) was stirred at 40°C for 4 days. In the reaction system was added water and the mixture was extracted with ethyl acetate. The organic layer p is washed with water and saturated salt solution and dried over magnesium sulfate. After concentration under reduced pressure the residue was separated and purified by chromatography on a column of silica gel (eluent: ethyl acetate:hexane=1:3→6:4) to obtain the specified title compound (637 mg) as a white solid.

1H-NMR (CDCl3) δ: 1,33 of 1.46 (2H, m), 1,61-1,72 (2H, m), 1,84-of 1.97 (2H, m), 2,04 (3H, c), of 4.05 (2H, t, J=6.6 Hz), 4,48 (2H, t, J=7.5 Hz), of 6.71 (1H, d, J=3.3 Hz), 7,46 (1H, d, J=3.3 Hz), 8,69 (1H, c).

(ii) Obtain 5-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]pentane-1-ol

A solution of 5-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)pistillata (200 mg) and 3-chloro-4-[3-(trifluoromethyl)phenoxy]aniline (265 mg) in isopropyl alcohol (3.5 ml) was stirred at 80°C for 14 hours was Added 1N. an aqueous solution of sodium hydroxide (2.1 ml) at 0°C and the mixture was stirred at room temperature for 1 h was Added to the reaction system 1H. hydrochloric acid (2.0 ml) and the mixture was extracted with ethyl acetate. The organic layer was washed with an aqueous solution of sodium bicarbonate and a saturated salt solution and dried over magnesium sulfate. After concentration under reduced pressure the residue was separated and purified by chromatography on a column of silica gel (eluent: ethyl acetate→ethyl acetate:methanol=1:19) to give a colorless solid. Recrystallization from a mixture of ethyl acetate-hexane gave specified in the title compound (275 the g) as colorless crystals.

1H-NMR (CDCl3) δ: 1,35 (1H, t, J=4,7 Hz), 1,50 was 1.69 (4H, m), 1,92-of 2.05 (2H, m), 3,63-3,71 (2H, m), 4,32 (2H, t, J=7.4 Hz), 6,59 (1H, d, J=3.3 Hz), 6,70 (1H, c), was 7.08 (1H, d, J=8.7 Hz), 7,09 for 7.12 (1H, m), 7,15-7,27 (2H, m), 7,30-to 7.35 (1H, m), 7,40-the 7.43 (1H, m), 7,47 (1H, DD, J=8,7, 2.7 Hz), 7,82 (1H, d, J=2.7 Hz), 8,53 (1H, c).

Example 155

Obtain N-{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}-2-hydroxyacetamido

(i) Obtain tert-butyl[2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethyl]carbamate

Specified in the title compound (687 mg) was obtained as a colourless solid interaction similar to the method of example 154 (i)using 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (0.50 g), tert-butyl-2-bromethylamine (0.95 g), cesium carbonate (1,59 g) and N,N-dimethylformamide (10 ml).

1H-NMR (CDCl3) δ: 1,31 of 1.46 (9H, m), 3,55 (2H, dt, J=6,0, 6,0 Hz), 4,51-and 4.68 (3H, m), 6,74 (1H, d, J=3.2 Hz), 7,47 (1H, d, J=3.2 Hz), 8,71 (1H, c).

(ii) Obtain tert-butyl{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}carbamate

A solution of tert-butyl[2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethyl]carbamate (712 mg) and 3-chloro-4-[3-(trifluoromethyl)phenoxy]aniline (830 mg) in isopropyl alcohol (7,1 ml) was stirred at 80°C for 12 h was Added to the reaction system aqueous sodium bicarbonate and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated solution of the m salt and dried over magnesium sulfate. After concentration under reduced pressure the residue was separated and purified by chromatography on a column of silica gel (eluent: hexane:ethyl acetate=1:1→ethyl acetate) to obtain the specified title compound (1.12 g) as colorless crystals.

1H-NMR (CDCl3) δ: for 1.49 (9H, c), 3,43-of 3.54 (2H, m), 4,43-4,51 (2H, m), 5,10 (1H, t, J=5.6 Hz), 6,60 (1H, d, J=3.3 Hz), 7,07 (1H, m), 7,09-7,14 (1H, m), 7,16-7,22 (2H, m), 7,25-7,30 (1H, m), 7,37 was 7.45 (1H, m), 7,89 (1H, DD, J=8,7, 2.4 Hz), 8,02 (1H, d, J=2,4 Hz)and 8.50 (1H, c)8,64 (1H, user. c).

(iii) Obtaining dihydrochloride 5-(2-amino-ethyl)-N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

A mixture of tert-butyl{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}carbamate (1.12 g), 2n. hydrochloric acid (15 ml) and tetrahydrofuran (30 ml) was stirred at 60°C for 20 hours, the Solvent is evaporated under reduced pressure, was added ethanol and the mixture is optionally concentrated. Precipitated precipitated crystals were separated by filtration and washed with ethyl acetate to obtain specified in the title compound (1.07 g) as pale yellow crystals.

1H-NMR (DMSO-d6) δ: 3,21-to 3.35 (2H, m), 4.92 in-5,02 (2H, m), of 6.71-6,76 (1H, m), 7.24 to to 7.32 (2H, m), 7,37 (1H, d, J=9.0 Hz), 7,50-7,56 (1H, m), of 7.64-7,71 (2H, m), to $ 7.91-of 7.97 (1H, m), 7,98-of 8.06 (1H, m), 8,13 compared to 8.26 (3H, m), 8,71 (1H, user. c)9,88-9,99 (1H, m).

(iv) Obtaining N-{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}2-hydroxyacetamido

The mixture of the dihydrochloride of 5-(2-amino-ethyl)-N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine (105 mg), glycolic acid (44 mg), hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (167 mg), monohydrate of 1-hydroxybenzotriazole (133 mg), triethylamine (0,40 ml) and N,N-dimethylformamide (5.0 ml) was stirred at room temperature for 3 days. Was added to the reaction system of water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated salt solution and dried over magnesium sulfate. After concentration under reduced pressure the residue was separated and purified by chromatography on a column with a basic silica gel (eluent: ethyl acetate→methanol:ethyl acetate=1:9) to obtain the specified title compound (108 mg) as colorless crystals.

1H-NMR (CDCl3) δ: 2,93-to 3.09 (1H, m), 3,59-to 3.73 (2H, m), 4,24 (2H, c), 4,43-a 4.53 (2H, m), 6,59 (1H, d, J=3.3 Hz), 7,07 (1H, d, J=8.7 Hz), 7,09-7,46 (6H, m), 7,72 (1H, DD, J=8,7, 2.4 Hz), of 8.06 (1H, d, J=2.4 Hz), 8,49 (1H, c)to 8.57 (1H, c).

Example 156

Obtain N-{2-[4-({3-chloro-4-[3-(triptoreline)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}-2-(methylsulphonyl)ndimethylacetamide

(i) Obtain tert-butyl{2-[4-({3-chloro-4-[3-(triptoreline)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}carbamate

A solution of tert-butyl[2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethyl]carbamate (100 m is), 3-chloro-4-[3-(triptoreline)phenoxy]aniline (153 mg) in isopropyl alcohol (1.5 ml) was stirred at 80°C for 12 h In the reaction system was added an aqueous solution of sodium bicarbonate and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated salt solution and dried over magnesium sulfate. After concentration under reduced pressure the residue was separated and purified by chromatography on a column of silica gel (eluent: hexane:ethyl acetate=1:1→ethyl acetate) to obtain the specified title compound (173 mg) as colorless crystals.

1H-NMR (CDCl3) δ: 1.50 in (9H, c), 3,45-of 3.54 (2H, m), 4,43-to 4.52 (2H, m), 5,01-5,08 (1H, m), is 6.61 (1H, d, J=3.0 Hz), 6,80-to 6.95 (3H, m), to 7.09 (1H, d, J=8.7 Hz), 7,19 (1H, d, J=3.0 Hz), 7,29-7,34 (1H, m), of 7.90 (1H, DD, J=8,7 with 2.7 Hz), 8,03 (1H, d, J=2.7 Hz), charged 8.52 (1H, c), to 8.62 (1H, user. c).

(ii) Obtaining dihydrochloride 5-(2-amino-ethyl)-N-{3-chloro-4-[3-(triptoreline)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

A mixture of tert-butyl{2-[4-({3-chloro-4-[3-(triptoreline)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}carbamate (173 mg), 2n. hydrochloric acid (2.5 ml) and tetrahydrofuran (5.0 ml) was stirred at 60°C for 6 hours was Added to the reaction system ethanol. The solvent is evaporated under reduced pressure. To the concentrate was added ethanol and the mixture is still concentrated under reduced pressure. The residual crystals were separated by filtration and washed what dilatatum obtaining specified in the title compound (155 mg) as pale-yellow crystals.

1H-NMR (DMSO-d6) δ: 3,21-to 3.34 (2H, m), 4,89-5,00 (2H, m), 6,74 (1H, d, J=2.4 Hz), 6,94-7,01 (2H, m), 7,16 (1H, d, J=8.7 Hz), was 7.36 (1H, d, J=9.0 Hz), 7,51-EUR 7.57 (1H, m), 7,62-of 7.69 (1H, m), of 7.90-of 7.95 (1H, m), 7,99-with 8.05 (1H, m,), 8,12-of 8.27 (3H, m), 8,71 (1H, c), 9,92 (1H, user. c).

(iii) Obtaining N-{2-[4-({3-chloro-4-[3-(triptoreline)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}-2-(methylsulphonyl)ndimethylacetamide

The mixture of the dihydrochloride of 5-(2-amino-ethyl)-N-{3-chloro-4-[3-(triptoreline)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine (160 mg), 2-(methylsulphonyl)acetic acid (82,3 mg), hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (171 mg), monohydrate of 1-hydroxybenzotriazole (137 mg), triethylamine (0,42 ml) and N,N-dimethylformamide (5,0 ml) was stirred at room temperature for 20 hours was Added to the reaction system of water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated salt solution and dried over magnesium sulfate. After concentration under reduced pressure the residue was separated and purified by chromatography on a column with a basic silica gel (eluent: ethyl acetate→ethyl acetate:methanol=4:1) and crystallization from a mixture of ethanol-ethyl acetate-diisopropyl ether to obtain specified in the title compound (112 mg) as pale-yellow crystals.

1H-NMR (CDCl3) δ: 3,12 (3H, c), 3,64 is 3.76 (2H, m)to 3.99 (2H, c), 4,34-to 4.52 (2H, m), 6,62 (1H, d, J=3.0 Hz), for 6.81-6,84 (1H, m), 6,86-to 6.95 (2H, m), was 7.08 (1H, d, J=8.7 Hz), 7,17-7,24 (2H, m), 7.29 trend to 7.4 (1H, m), 7,76 (1H, DD, J=8,7, 2.7 Hz), 7,95 (1H, d, J=2.7 Hz), 8,18 (1H, c), 8,51 (1H, c).

Melting point: 133-135°C.

Example 157

Obtain N-{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}-2-methoxyacetate

Specified in the title compound (120 mg) was obtained as colorless crystals by the interaction is similar to the method of example 155 (iv)using dihydrochloride of 5-(2-amino-ethyl)-N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine (150 mg), methoxybutanol acid (52 mg), hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (166 mg), monohydrate 1-of hydroxybenzotriazole (133 mg), triethylamine (0,40 ml) and N,N-dimethylformamide (5.0 ml).

1H-NMR (CDCl3) δ: 3,44 (3H, c), 3,60-3,71 (2H, m)4,00 (2H, c), of 4.44-a 4.53 (2H, m), 6,62 (1H, d, J=3.0 Hz), 7,02-to 7.15 (3H, m), 7,19 (1H, d, J=3.0 Hz), 7,22-to 7.35 (2H, m), 7,38 was 7.45 (1H, m), 7,74 (1H, DD, J=8,7, 2.4 Hz), 8,07 (1H, d, J=2.4 Hz), charged 8.52 (1H, c), 8,55 (1H, c).

Example 158

Obtain N-{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}-3-hydroxy-3-methylbutanoic

The mixture of the dihydrochloride of 5-(2-amino-ethyl)-N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine (150 mg), 3-hydroxy-3-methylmalonic acid (68 mg), hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (166 mg), monohydrate of 1-hydroxybenzotriazole(133 mg), triethylamine (0,40 ml) and N,N-dimethylformamide (5.0 ml) was stirred at room temperature for 5 days. Was added to the reaction system of water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated salt solution and dried over magnesium sulfate. After concentration under reduced pressure the residue was separated and purified by chromatography on a column with a basic silica gel (eluent: ethyl acetate→ethyl acetate:methanol=9:1). Crystallization from a mixture of ethyl acetate-diisopropyl ether gave specified in the title compound (122 mg) as colorless crystals.

1H-NMR (CDCl3) δ: of 1.33 (6H, c), 2,49 (2H, c), 2,65-2,77 (1H, m), 3,57-3,68 (2H, m), of 4.44-a 4.53 (2H, m), is 6.61 (1H, d, J=3.0 Hz), 6,93-7,01 (1H, m), 7,07 (1H, d, J=9.0 Hz), 7,09-to 7.15 (1H, m), 7,19 (1H, d, J=3.0 Hz), 7.23 percent-to 7.35 (2H, m), 7,40 was 7.45 (1H, m), to 7.77 (1H, DD, J=9,0, 2.7 Hz), 8,08 (1H, d, J=2.7 Hz), charged 8.52 (1H, c), 8,66 (1H, c).

Melting point: 167-169°C.

Example 159

Obtain N-{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}-2-hydroxy-2-methylpropanamide

To a suspension of the hydrochloride 5-(2-amino-ethyl)-N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine (150 mg) and triethylamine (0,40 ml) in tetrahydrofuran (5.0 ml) was added 1-chlorocarbonyl-1-methylethylacetate (0,12 ml) at room temperature. After stirring at room temperature for stock, was added an aqueous solution of sodium bicarbonate and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over magnesium sulfate and concentrated under reduced pressure. To a solution of the residue in ethanol (3.0 ml) was added 1N. an aqueous solution of sodium hydroxide (1.5 ml) at room temperature. After stirring at room temperature for 24 h, the mixture was extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over magnesium sulfate, concentrated under reduced pressure, the residue was separated and purified by chromatography on a column with a basic silica gel (eluent: ethyl acetate→ethyl acetate:methanol=9:1) to obtain the specified title compound (133 mg) as colorless crystals.

1H-NMR (CDCl3) δ: 1,49 (6H, c), 2,12-of 2.27 (1H, m), 3,56-to 3.67 (2H, m), 4,42-to 4.52 (2H, m), is 6.61 (1H, d, J=3.3 Hz), 7,06 (1H, d, J=9.0 Hz), 7,08-7,14 (1H, m), 7,15-the 7.43 (5H, m), 7,86 (1H, DD, J=9,0, 2.7 Hz), 8,10 (1H, d, J=2.7 Hz), 8,51 (1H, c), 8,72 (1H, c).

Example 160

Obtain N-{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}-2-(methylsulphonyl)ndimethylacetamide

The mixture of the dihydrochloride of 5-(2-amino-ethyl)-N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine (150 mg), 2-(methylsulphonyl)acetic acid (to 79.6 mg), hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl carb is diimide (166 mg), monohydrate of 1-hydroxybenzotriazole (133 mg), triethylamine (0,40 ml) and N,N-dimethylformamide (5.0 ml) was stirred at room temperature for 20 hours was Added to the reaction system of water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated salt solution and dried over magnesium sulfate. After concentration under reduced pressure the residue was separated and purified by chromatography on a column with a basic silica gel (eluent: ethyl acetate→ethyl acetate:methanol=4:1). Crystallization from a mixture of ethyl acetate-diisopropyl ether gave specified in the title compound (128 mg) as colorless powdery crystals.

1H-NMR (CDCl3) δ: 3,12 (3H, c), 3,64 of 3.75 (2H, m), 3,98 (2H, c), 4,43-a 4.53 (2H, m), 6,62 (1H, d, J=3.0 Hz), 7,07 (1H, d, J=9.0 Hz), 7,09-to 7.15 (1H, m), 7.18 in-7,33 (4H, m), 7,40 was 7.45 (1H, m), to 7.77 (1H, DD, J=9,0, 2.7 Hz), of 7.96 (1H, d, J=2.7 Hz), 8,19 (1H, c), 8,51 (1H, c).

Melting point: 177-178°C.

Example 161

Getting 5-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]-3-methylpentane-1,3-diol

(i) Obtaining 3,5-dihydroxy-3-methylpentanoate

A solution of 3-methyl-1,3,5-pentandiol (21,9 g), benzoic anhydride (7,39 g), pyridine (4.0 ml) and 4-(N,N-dimethylamino)pyridine (0.39 g) in acetonitrile (200 ml) was stirred at room temperature for 2 days. After concentration under reduced pressure, the AI was added water and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over magnesium sulfate, concentrated under reduced pressure, the residue was separated and purified by chromatography on a column of silica gel (eluent: hexane:ethyl acetate=1:1→ethyl acetate) to obtain specified in the connection header (4,27 g) as a colourless oil.

1H-NMR (CDCl3) δ: 1,36 (3H, c), 1,72-of 1.81 (1H, m), of 1.86 and 2.13 (3H, m), 2,47 (1H, t, J=4,7 Hz), 2,89 (1H, c), 3,85-was 4.02 (2H, m)to 4.52 (2H, t, J=6.8 Hz), 7,42-of 7.48 (2H, m), 7,54-of 7.60 (1H, m), 8,00-of 8.04 (2H, m).

(ii) Obtain 5-bromo-3-hydroxy-3-methylpentanoate

To a solution of 3,5-dihydroxy-3-methylpentanoate (1.0 g) and tetrabromide carbon (2,78 g) in tetrahydrofuran (30 ml) was added dropwise a solution of triphenylphosphine (2.20 g) in tetrahydrofuran (10 ml) under cooling with ice. After stirring at room temperature for 3 days was added water and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over magnesium sulfate, concentrated under reduced pressure, the residue was separated and purified by chromatography on a column of silica gel (eluent: hexane:ethyl acetate=9:1→6:4) to obtain specified in the connection header (979 mg) as a colourless oil.

1H-NMR (CDCl3) δ: 1,32 (3H, c), of 1.78 (1H, c), 1,97-2,02 (2H, m), 2,11-of 2.23 (2H, m), 3,53 (2H, t, J=8.1 Hz), 4,51 (2H, t, J=6.5 Hz), 7,42-of 7.48 (2H, m), 7,55-of 7.60 (1H, m), 8,00-of 8.04 (2H, m).

(iii) Obtaining 5-(4-chloro-5H-Pierre is lo[3,2-d]pyrimidine-5-yl)-3-hydroxy-3-methylpentanoate

Specified in the title compound (773 mg) was obtained as a colourless oil interaction, analogous to the methods of example 154 (i)using 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (400 mg), 5-bromo-3-hydroxy-3-methylpentanoate (979 mg), cesium carbonate (0,94 g) and N,N-dimethylformamide (10 ml).

1H-NMR (CDCl3) δ: of 1.41 (3H, c), at 1.91 (1H, c), 2,01 and 2.13 (4H, m), of 4.54 (2H, t, J=6.6 Hz), 4,59 was 4.76 (2H, m), of 6.71 (1H, d, J=3.0 Hz), 7,40-7,46 (2H, m), 7,51 (1H, d, J=3.0 Hz), 7,54-of 7.60 (1H, m), 7,98 shed 8.01 (2H, m), 8,69 (1H, c).

(iv) Obtain 5-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]-3-methylpentane-1,3-diol

Specified in the title compound (223 mg) was obtained as colorless crystals by the interaction analogous to the methods of example 154 (ii)using 5-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)-3-hydroxy-3-methylpentanoate (250 mg), 3-chloro-4-[3-(trifluoromethyl)phenoxy]aniline (230 mg), isopropyl alcohol (1.5 ml) and 1N. an aqueous solution of sodium hydroxide (2.0 ml).

1H-NMR (CDCl3) δ: of 1.35 (3H, c), 1,62-1,71 (1H, m), 1,89-2,22 (4H, m), 3,93-4,18 (2H, m), 4,54 with 4.65 (3H, m), 6,56 (1H, d, J=3.0 Hz),? 7.04 baby mortality (1H, d, J=8.7 Hz), 7,08-7,14 (1H, m), 7,19-of 7.25 (2H, m), 7,29-to 7.35 (1H, m), 7,39-7,44 (1H, m), to 7.61 (1H, DD, J=8,7, 2.7 Hz), to 7.93 (1H, d, J=2.7 Hz), 8,49 (1H, c), charged 8.52 (1H, user. c).

Example 162

Getting 2-({2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}thio)ethanol

(i) Obtaining 2-[(2-hydroxyethyl)thio]this is benzoate

A solution of 2-mercaptoethanol (1,52 ml), 2-icatibant (6,00 g) and ethyldiethanolamine (4,53 ml) in N,N-dimethylformamide (60 ml) was stirred at 40°C for 3 days. Was added to the reaction system and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by chromatography on a column of silica gel (eluent: hexane:ethyl acetate=4:1→3:7) to obtain the specified title compound (3.77 g) as orange oil.

1H-NMR (CDCl3) δ: 2,15 (1H, t, J=6.0 Hz), and 2.83 (2H, t, J=5,9 Hz), of 2.92 (2H, t, J=6.8 Hz), with 3.79 (2H, dt, J=6,0, 6,0 Hz), 4,50 (2H, t, J=6.8 Hz), 7,43-of 7.48 (2H, m), 7,55-to 7.61 (1H, m), 8,03-8,08 (2H, m).

(ii) Obtaining 2-[(2-bromacil)thio]ethylbenzoic

Specified in the header connection (966 mg) was obtained as a colourless oil interaction, analogous to the methods of example 161 (ii)using 2-[(2-hydroxyethyl)thio]ethylbenzoic (1.0 g), tetrabromide carbon (2.20 g), triphenylphosphine (1,74 g) and dichloromethane (50 ml).

1H-NMR (CDCl3) δ: 2,95 (2H, t, J=6.8 Hz), 3,02-is 3.08 (2H, m), 3,50 of 3.56 (2H, m), of 4.49 (2H, t, J=6.8 Hz), 7,43-of 7.48 (2H, m), 7,55-to 7.61 (1H, m), 8,03-of 8.06 (2H, m).

(iii) Obtaining 2-{[2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethyl]thio}ethylbenzoic

Specified in the title compound (790 mg) was obtained as a colourless oil interaction by a similar method the sample is 154 (i), using 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (420 mg), 2-[(2-bromacil)thio]ethylbenzoic (966 mg), cesium carbonate (1,34 g) and N,N-dimethylformamide (4,2 ml).

1H-NMR (CDCl3) δ: of 2.81 (2H, t, J=6.8 Hz), is 3.08 (2H, t, J=6.9 Hz), of 4.45 (2H, t, J=6.8 Hz), 4,69 (2H, t, J=6.9 Hz), was 6.73 (1H, d, J=3.3 Hz), 7,39-7,46 (2H, m), 7,53 to 7.62 (2H, m), of 7.96-of 8.06 (2H, m), 8,71 (1H, c).

(iv) Obtaining 2-({2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}thio)ethanol

Specified in the title compound (420 mg) was obtained as colorless crystals by the interaction analogous to the methods of example 154 (ii)using 2-{[2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethyl]thio}etilbenzene (505 mg), 3-chloro-4-[3-(trifluoromethyl)phenoxy]aniline (480 mg), isopropyl alcohol (10 ml) and 1N. an aqueous solution of sodium hydroxide (3.0 ml).

1H-NMR (CDCl3) δ: 1,92 is 2.00 (1H, m), 2,52 (2H, t, J=5.6 Hz), of 3.13 (2H, t, J=6.5 Hz), 3,65 of 3.75 (2H, m), br4.61 (2H, t, J=6.5 Hz), to 6.67 (1H, d, J=3.3 Hz), was 7.08 (1H, d, J=8.7 Hz), 7,09-7,13 (1H, m), 7.18 in-of 7.23 (1H, m), 7,29 (1H, d, J=3.3 Hz), 7,32-to 7.35 (1H, m), 7,41-7,46 (1H, m), 7,51 (1H, DD, J=8,7, 2.7 Hz), to 7.77 (1H, d, J=2.7 Hz), 7,80 (1H, c), 8,55 (1H, c).

Example 163

Obtain N-{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}-N-methyl-2-(methylsulphonyl)ndimethylacetamide

(i) Obtain tert-butyl[2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethyl]methylcarbamate

To a solution of 2-(methylamino)ethanol (1,00 g) in tetrahydrofuran (10 ml) EXT is ulali di-tert-butyl dicarbonate (3,60 ml) at room temperature. After stirring at room temperature for 2 h, the mixture was concentrated under reduced pressure. To a solution of the residue and triethylamine (3,71 ml) in tetrahydrofuran (50 ml) was added dropwise methanesulfonanilide (1,55 ml) at 0°C and the mixture was stirred at 0°C for 1 h was Added to the reaction system an aqueous solution of sodium bicarbonate and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over magnesium sulfate and concentrated under reduced pressure to obtain a colorless oil. Specified in the title compound (902 mg) was obtained as a pale yellow oil interaction, analogous to the methods of example 154 (i), using the obtained oil, 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (1,34 g), cesium carbonate (5,69 g) and N,N-dimethylformamide (20 ml).

1H-NMR (CDCl3) δ: 1,12 (4,5H, c), 1,43 (4,5H, m), 2,55 (1,5H, c)2,81 (1,5H, c), to 3.58-of 3.60 (2H, m), 4,54-4,69 (2H, m), of 6.73 (1H, d, J=3.0 Hz), 7,29-7,35 (0,5H, m), 7,38-7,46 (0,5H, m), 8,71 (1H, c).

(ii) Obtain tert-butyl{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}methylcarbamate

Specified in the title compound (622 mg) was obtained as a colorless amorphous solid interaction similar to the method of example 155 (ii)using tert-butyl[2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethyl]methylcarbamate (450 mg), 3-chloro-4-[3-(t is iformity)phenoxy]aniline (500 mg) and isopropyl alcohol (4.5 ml).

1H-NMR (CDCl3) δ: rate of 1.51 (9H, c), a 3.01 (3H, c), 3,51-3,59 (2H, m), to 4.41-4,51 (2H, m), 6,60 (1H, d, J=3.0 Hz), 7,06 (1H, d, J=8.7 Hz), 7,08-7,13 (1H, m), 7,15-7,24 (2H, m), 7,30 (1H, d, J=8,4 Hz), 7,38-7,44 (1H, m), a 7.85-to 7.93 (1H, m), 7,99-of 8.04 (1H, m), and 8.50 (1H, c), 8,82 (1H, c).

(iii) obtaining the dihydrochloride of N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5-[2-(methylamino)ethyl]-5H-pyrrolo[3,2-d]pyrimidine-4-amine

Specified in the title compound (538 mg) was obtained as pale-yellow crystals by the interaction is similar to the method of example 155 (iii)using tert-butyl{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}methylcarbamate (622 mg), 2n. hydrochloric acid (10 ml) and tetrahydrofuran (20 ml).

1H-NMR (DMSO-d6) δ: 2,54 (3H, t, J=5.3 Hz), 3,32-3,44 (2H, m), 5,01-of 5.15 (2H, m), 6,74 (1H, d, J=3.3 Hz), 7,22-7,27 (2H, m), of 7.36 (1H, d, J=8.7 Hz), 7,51 (1H, d, J=8,4 Hz), 7,60-of 7.69 (2H, m), to $ 7.91-of 7.96 (1H, m), 8,01-8,07 (1H, m), 8,72 (1H, c), 9,00-9,18 (2H, m), 10,06 (1H of user. c).

(iv) Obtaining N-{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}-N-methyl-2-(methylsulphonyl)ndimethylacetamide

Specified in the title compound (131 mg) was obtained as colorless crystals by the interaction is similar to the method of example 155 (iv)using dihydrochloride of N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5-[2-(methylamino)ethyl]-5H-pyrrolo[3,2-d]pyrimidine-4-amine (170 mg), 2-(methylsulphonyl)acetic acid (88 mg), hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl the Il)carbodiimide (183 mg), monohydrate of 1-hydroxybenzotriazole (146 mg), triethylamine (of 0.44 ml) and N,N-dimethylformamide (5.0 ml).

1H-NMR (CDCl3) δ: 3,17 (3H, c)to 3.34 (3H, c), 3,75-a-3.84 (2H, m), 4,18 (2H, c), 4,43-to 4.52 (2H, m), only 6.64 (1H, d, J=3.0 Hz), was 7.08 (1H, d, J=8.7 Hz), 7,10-7,16 (1H, m), 7,17-of 7.25 (2H, m), 7,32-7,37 (1H, m), 7,41-7,46 (1H, m,), 7,86 (1H, DD, J=8,7, 2.7 Hz), of 7.96 (1H, d, J=2.7 Hz), 8,46 (1H, c), 8,53 (1H, c).

Example 164

Getting 2-({2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}sulfinil)ethanol

To a solution of 2-({2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}thio)ethanol (100 mg) in dichloromethane (10 ml) was added dropwise 70% solution of 3-chloroperbenzoic acid (58 mg) in dichloromethane (5.0 ml) -78°C. the Mixture was stirred at -78°C for 1 h and was added an aqueous solution of sodium thiosulfate. After stirring at room temperature for 0.5 h the mixture was extracted with ethyl acetate. The organic layer was washed with saturated salt solution and dried over magnesium sulfate. After concentration under reduced pressure the residue was separated and purified by chromatography on a column of silica gel (eluent: ethyl acetate→ethyl acetate:methanol=4:1) to obtain the specified title compound (87 mg) as colorless crystals.

1H-NMR (DMSO-d6) δ: 2,78-a 3.01 (2H, m), 3.27 to is 3.40 (1H, m), 3,42-to 3.58 (1H, m), 3,71-with 3.79 (2H, m), 4.80 to the 4.90 (2H, m), 5,02-5,09 (1H, m), 6,58-6,63 (1H, m), 7,16-7,25 2H, m), 7,27-7,31 (1H, m), 7,44 is 7.50 (1H, m), to 7.59-to 7.64 (1H, m), 7,66-7,72 (1H, m), 7,74-of 7.82 (1H, m), of 7.96-8,03 (1H, m), of 8.37 (1H, c), 9,38 (1H, c).

Example 165

Getting 2-({2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}sulfonyl)ethanol

To a solution of 2-({2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}thio)ethanol (150 mg), tetraisopropoxide titanium (43 μl), methanol (24 ml) and water (10 μl) in dichloromethane was stirred at room temperature for 30 minutes In the reaction system was added 70% aqueous solution of tert-butylhydroperoxide (0,12 ml) and the mixture was stirred at room temperature for 2 days. In the reaction system was added aqueous sodium thiosulfate solution and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over magnesium sulfate, concentrated under reduced pressure, the residue was separated and purified by chromatography on a column of silica gel (eluent: ethyl acetate→ethyl acetate:methanol=4:1) to obtain the specified title compound (118 mg) as colorless crystals.

1H-NMR (DMSO-d6) δ: 3,09 is 3.15 (2H, m), 3,62 of 3.75 (4H, m), 4.92 in-5,02 (2H, m), 5,09-of 5.15 (1H, m), 6,50-to 6.57 (1H, m), 7,16-to 7.32 (3H, m), 7,45-of 7.48 (1H, m), 7,58-7,74 (3H, m), to $ 7.91-of 7.97 (1H, m), of 8.37 (1H, user. c)8,69-8,79 (1H, m).

Example 166

Obtain N-{2-[4-({3-PI is the p-4-[3-(triptoreline)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}-N-methyl-2-(methylsulphonyl)ndimethylacetamide

(i) Obtain tert-butyl{2-[4-({3-chloro-4-[3-(triptoreline)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}methylcarbamate

Specified in the title compound (665 mg) was obtained as a colorless amorphous solid interaction similar to the method of example 155 (ii)using tert-butyl[2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethyl]methylcarbamate (463 mg), 3-chloro-4-[3-(triptoreline)phenoxy]aniline (679 mg) and isopropyl alcohol (5.0 ml).

1H-NMR (CDCl3) δ: rate of 1.51 (9H, c), a 3.01 (3H, c), 3,48-3,61 (2H, m), 4,42-4,50 (2H, m), 6,60 (1H, d, J=3.2 Hz), 6,80-6,83 (1H, m), 6,86-to 6.95 (2H, m), was 7.08 (1H, d, J=8.7 Hz), 7,20 (1H, d, J=3.2 Hz), 7,28-7,33 (1H, m), a 7.85-of 7.95 (1H, m), 7,99-with 8.05 (1H, m), 8,51 (1H, c), 8,81 (1H, user. c).

(ii) obtaining the dihydrochloride of N-{3-chloro-4-[3-(triptoreline)phenoxy]phenyl}-5-[2-(methylamino)ethyl]-5H-pyrrolo[3,2-d]pyrimidine-4-amine

Specified in the title compound (557 mg) was obtained as pale-yellow crystals by the interaction is similar to the method of example 155 (iii)using tert-butyl{2-[4-({3-chloro-4-[3-(triptoreline)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}methylcarbamate (665 mg), 2n. hydrochloric acid (10 ml) and tetrahydrofuran (20 ml).

1H-NMR (DMSO-d6) δ: 2,52-of 2.66 (2H, m)), 3,29 is-3.45 (2H, m), 5,03-of 5.15 (2H, m), of 6.75 (1H, d, J=3.0 Hz), 6,91-7,00 (2H, m), 7,11-to 7.18 (1H, m), 7,35 (1H, d, J=8.7 Hz), 7,51-EUR 7.57 (1H, m), 7,63-of 7.69 (1H, m), to $ 7.91-of 7.96 (1H, m), of 8.06 (1H, d, J=3.3 Hz), 8,73 (1H, c), 9,06-9,26 (2H, m), 10,11 (1H, user. c).

(iii) Receive is of N-{2-[4-({3-chloro-4-[3-(triptoreline)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}-N-methyl-2-(methylsulphonyl)ndimethylacetamide

Specified in the title compound (147 mg) was obtained as colorless crystals by the interaction is similar to the method of example 155 (iv)using dihydrochloride of N-{3-chloro-4-[3-(triptoreline)phenoxy]phenyl}-5-[2-(methylamino)ethyl]-5H-pyrrolo[3,2-d]pyrimidine-4-amine (170 mg), 2-(methylsulphonyl)acetic acid (87 mg), hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (179 mg), monohydrate of 1-hydroxybenzotriazole (143 mg), triethylamine (0,43 ml) and N,N-dimethylformamide (5.0 ml).

1H-NMR (CDCl3) δ: 3,17 (3H, c)to 3.34 (3H, c), 3,75-a-3.84 (2H, m), 4,18 (2H, c), 4,43-to 4.52 (2H, m), only 6.64 (1H, d, J=3.0 Hz), was 7.08 (1H, d, J=8.7 Hz), 7,10-7,16 (1H, m), 7,17-of 7.25 (2H, m), 7,32-7,37 (1H, m), 7,41-7,46 (1H, m,), 7,86 (1H, d, J=8,7, 2.7 Hz), of 7.96 (1H, d, J=2.7 Hz), 8,46 (1H,c), 8,53 (1H, c).

Example 167

Obtain hydrochloride of N-{3-[4-({3-chloro-4-[3-(triptoreline)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]propyl}-2-(methylsulphonyl)ndimethylacetamide

(i) Obtain tert-butyl[3-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)propyl]carbamate

Specified in the title compound (1.04 g) was obtained as a colourless oil interaction, analogous to the methods of example 154 (i)using 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (500 mg), tert-butyl 3-bromopropionate (1,00 g), cesium carbonate (1,59 g) and N,N-dimethylacetamide (5.0 ml).

1H-NMR (CDCl3) δ: of 1.46 (9H, c), 2,02-2,12 (2H, m), 3,13-of 3.25 (2H, m), 4,50-of 4.66 (3H, m), is 6.78 (1H, d, J=3.0 Hz), to 7.61-of 7.69 (1H, m), 8,71 (H, c).

(ii) Obtain tert-butyl{3-[4-({3-chloro-4-[3-(triptoreline)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]propyl}carbamate

Specified in the title compound (398 mg) was obtained as a colorless amorphous solid interaction similar to the method of example 155 (ii)using tert-butyl[3-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)propyl]carbamate (546 mg), 3-chloro-4-[3-(triptoreline)phenoxy]aniline (640 mg) and isopropyl alcohol (10 ml).

1H-NMR (CDCl3) δ: of 1.42 (9H, c), 2,10-of 2.21 (2H, m), 3,17-of 3.27 (2H, m), and 4.40 (2H, t, J=7.5 Hz), 4,69-rate 4.79 (1H, m), 6,62 (1H, d, J=3.0 Hz), for 6.81 (1H, user. c), 6,85-to 6.95 (2H, m),? 7.04 baby mortality-7,13 (2H, m), 7,29-7,34 (2H, m), 7,54-of 7.60 (1H, m), 7,89 (1H, d, J=3.0 Hz), charged 8.52 (1H, c).

(iii) Obtaining dihydrochloride 5-(3-aminopropyl)-N-{3-chloro-4-[3-(triptoreline)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

Specified in the title compound (355 mg) was obtained as colorless powder crystals by the interaction is similar to the method of example 155 (iii)using tert-butyl{3-[4-({3-chloro-4-[3-(triptoreline)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]propyl}carbamate (398 mg), 2n. hydrochloric acid (10 ml) and tetrahydrofuran (20 ml).

1H-NMR (DMSO-d6) δ: 2,03-of 2.16 (2H, m), 2,61 is 2.75 (2H, m), a 4.86 (2H, t, J=6.6 Hz), 6,70 (1H, d, J=3.0 Hz), 6,94-7,01 (2H, m), 7,11-7,19 (1H, m), 7,37 (1H, d, J=8.7 Hz), 7,52-7,58 (1H, m), to 7.67 (1H, DD, J=8,7, 2.7 Hz), 7,95 (1H, d, J=2.1 Hz), of 7.96-815 (4H, m), 8,72 (1H, c), 9,96 (1H, user. c).

(iv) Obtaining the of hydrochloride N-{3-[4-({3-chloro-4-[3-(triptoreline)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]propyl}-2-(methylsulphonyl)ndimethylacetamide

N-{3-[4-({3-Chloro-4-[3-(triptoreline)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]propyl}-2-(methylsulphonyl)ndimethylacetamide was obtained by interaction similar to the method of example 155 (iv)using dihydrochloride of 5-(3-aminopropyl)-N-{3-chloro-4-[3-(triptoreline)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine (170 mg), 2-(methylsulphonyl)acetic acid (85,0 mg), hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (177 mg), monohydrate of 1-hydroxybenzotriazole (141 mg), triethylamine (0,43 ml) and N,N-dimethylformamide (5.0 ml). To a solution of N-{3-[4-({3-chloro-4-[3-(triptoreline)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]propyl}-2-(methylsulphonyl)ndimethylacetamide in ethyl acetate (1.0 ml) was added a mixture of 4h. hydrochloric acid-ethyl acetate (0,50 ml) at room temperature and the mixture was stirred at room temperature for 1 h After concentration under reduced pressure was added diisopropyl ether and precipitated precipitated crystals were separated by filtration. The crystals are washed with diisopropyl ether to obtain specified in the title compound (128 mg) as colorless powdery crystals.

1H-NMR (DMSO-d6) δ: 1,88 is 2.00 (2H, m), 2,97-is 3.08 (2H, m), 3,11 (3H, c), Android 4.04 (2H, c), 4,63-4,72 (2H, m), to 6.67 (1H, d, J=3.0 Hz), 6,94-7,01 (2H, m), 7,13-7,21 (1H, m), of 7.36 (1H, d, J=9.0 Hz), 7,49-the 7.65 (2H, m), to $ 7.91 (1H, d, J=2.4 Hz), of 7.96 (1H, d, J=3.0 Hz), 8,45-charged 8.52 (1H, m), to 8.70 (1H, c), 9,67 (1H, user. c).

Example 168

Obtain N-{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}-3-(methylsulphonyl)propanamide

(i) Obtaining N-{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}-3-(methylthio)propanamide

To a mixture of the dihydrochloride of 5-(2-amino-ethyl)-N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine (230 mg) and triethylamine (and 0.61 ml) in tetrahydrofuran (8.0 ml) was added 3-(methylthio)propionate (0.15 ml) under ice cooling. After stirring at room temperature for 20 h was added water and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over magnesium sulfate, concentrated under reduced pressure, the residue was separated and purified by chromatography on a column with a basic silica gel (eluent: ethyl acetate→ethyl acetate:methanol=9:1) to obtain the specified title compound (133 mg) as colorless crystals.

1H-NMR (CDCl3) δ: 2,13(3H, c)at 2.59 (2H, t, J=6.9 Hz), and 2.83 (2H, t, J=6.9 Hz), 3,57 at 3.69 (2H, m), 4,45-4,55 (2H, m), 6,39-6,47 (1H, m), 6,62 (1H, d, J=3.0 Hz), was 7.08 (1H, d, J=8.7 Hz), 7,09-7,14 (1H, m), 7,20 (1H, d, J=3.0 Hz), 7.23 percent-7,27 (1H, m), 7,29-7,34 (1H, m), 7,39-7,47 (1H, m), 7,83 (1H, DD, J=8,7, 2.7 Hz), to 8.12 (1H, d, J=2.7 Hz), 8,523 (1H, c), 8,63 (1H, c).

(ii) Obtaining N-{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}-3-(methylsulphonyl)PR is palamida

Specified in the title compound (97 mg) was obtained as colorless crystals by the interaction analogous to the methods of example 165, using N-{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}-3-(methylthio)propanamide (150 mg), tetraisopropoxide titanium (40,3 μl), methanol (22,2 mm), water (9,3 ml), 70% aqueous solution of tert-butylhydroperoxide (0,12 ml) and dichloromethane (8.0 ml).

1H-NMR (DMSO-d6) δ: 2,41-to 2.57 (2H, m), 2,95 (3H, c), 3,26 (2H, t, J=7.5 Hz), 3,35 is-3.45 (2H, m), 4,48-4,58 (2H, m), 6,51 (1H, d, J=3.0 Hz), 7.18 in-to 7.32 (3H, m), 7,43-7,50 (1H, m), 7,58-to 7.67 (2H, m), 7,73-of 7.82 (1H, m), 8,02-8,07 (1H, m), 8.34 per-to 8.45 (2H, m), is 8.75 (1H, c).

Example 169

Obtain N-{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}-2-methyl-2-(methylsulphonyl)propanamide

To a solution of 2-methyl-2-(methylsulphonyl)propanoic acid (115 mg) and N,N-dimethylformamide (catalytic amount) in tetrahydrofuran (5.0 ml) was added thionyl chloride (0.10 ml) at room temperature. After stirring at room temperature for 3 h the mixture was concentrated under reduced pressure. A solution of the residue in tetrahydrofuran (10 ml) was added dropwise to a suspension of the hydrochloride 5-(2-amino-ethyl)-N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine (180 mg) and triethylamine (of 0.48 ml) in tetrahydrofuran (10 ml) at room is temperature. After stirring at room temperature for 20 h, the reaction system was added water and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by chromatography on a column with a basic silica gel (eluent: ethyl acetate→ethyl acetate:methanol=9:1) to obtain the specified title compound (205 mg) as colorless crystals.

1H-NMR (CDCl3) δ: 1,70 (6H, c), with 2.93 (3H, c), 3,63-to 3.73 (2H, m), 4,43-to 4.52 (2H, m), only 6.64 (1H, d, J=3.3 Hz), to 7.09 (1H, d, J=8.7 Hz), 7,10-7,16 (1H, m), 7.18 in-7,24 (2H, m), 7,27-to 7.35 (2H, m), 7,40-7,47 (1H, m), of 7.90 (1H, DD, J=8,7, 2.7 GHz), with 8.05 (1H, d, J=2.7 Hz), scored 8.38 (1H, c), 8,54 (1H, c).

Melting point: 167-168°C.

Example 170

Obtain N-{2-[4-({3-chloro-4-[3-(triptoreline)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}-2-methyl-2-(methylsulphonyl)propanamide

To a solution of 2-methyl-2-(methylsulphonyl)propanoic acid (92 mg) and N,N-dimethylformamide (catalytic amount) in tetrahydrofuran (5.0 ml) was added thionyl chloride (80 μl) at room temperature. After stirring at room temperature for 3 h the mixture was concentrated under reduced pressure. A solution of the residue in a mixture of tetrahydrofuran-dichloromethane (10 ml-10 ml) was added dropwise to a suspension of the hydrochloride 5-(2-aminoet the)-N-{3-chloro-4-[3-(triptoreline)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine (150 mg) and triethylamine (0,39 ml) in tetrahydrofuran (10 ml) at room temperature. After stirring at room temperature for 20 h, was added to the reaction system an aqueous solution of sodium bicarbonate and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by chromatography on a column with a basic silica gel (eluent: ethyl acetate→ethyl acetate:methanol=9:1) to obtain the specified title compound (108 mg) as pale-yellow crystals.

1H-NMR (CDCl3) δ: 1,70 (6H, c), with 2.93 (3H, c), 3,62-to 3.73 (2H, m), 4,42-4,51 (2H, m), only 6.64 (1H, d, J=3.3 Hz), 6,82-6,86 (1H, m), 6,88-of 6.96 (2H, m), to 7.09 (1H, d, J=9.0 Hz), 7,21 (1H, d, J=3.3 Hz), 7,26-to 7.35 (2H, m), 7,89 (1H, DD, J=9,0, 2.6 Hz), of 8.04 (1H, d, J=2.6 Hz), of 8.37 (1H, c), 8,54 (1H, c).

Example 171

Obtain hydrochloride of N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5-[2-(2-methoxyethoxy)ethyl]-5H-pyrrolo[3,2-d]pyrimidine-4-amine

4-Chloro-5H-pyrrolo[3,2-d]pyrimidine (500 mg) was dissolved in N,N-dimethylformamide (10 ml) was added potassium carbonate (830 mg) and 2-(2-methoxyethoxy)ethyl-4-methylbenzenesulfonate (920 mg) and the mixture was stirred at room temperature for 12 hours To the reaction mixture were added saturated aqueous sodium hydrogen carbonate solution under ice cooling and the mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated. The mod is to was purified by chromatography on a column of silica gel (eluent: hexane:ethyl acetate=50:50→0:100). The resulting oil was dissolved in isopropyl alcohol (10 ml) was added 3-chloro-4-[3-(trifluoromethyl)phenoxy]aniline. The mixture was stirred at 90°C for 4 h, was added to the reaction mixture, saturated aqueous sodium hydrogen carbonate solution under ice cooling and the mixture was extracted with ethyl acetate. The extract was dried over magnesium sulfate and concentrated. The residue was separated and purified by chromatography on a column of silica gel (eluent: ethyl acetate:methanol=100:0→ethyl acetate:methanol=90:10) and was led from a mixture of 4h. an ethyl acetate solution of hydrochloric acid-hexane to obtain specified in the title compound (277 mg).

1H-NMR(DMSO-d6) δ: 3,06 (3H, c), 3,33-to 3.35 (2H, m), 3,55-3,61 (2H, m), 3,83-3,86 (2H, m), a 4.83-a 4.86 (2H, m), of 6.71 (1H, d, J=3 Hz), 7.24 to 7,72 (7H, m), 7,99-of 8.04 (2H, m), 8,77 (1H, c), 9,92 (1H, c).

Example 172

Obtain N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5-{2-[2-(methylsulphonyl)ethoxy]ethyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

(i) Obtaining N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5-{2-[2-(methylthio)ethoxy]ethyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

The compound (150 mg) of example 147 was dissolved in tetrahydrofuran (10 ml), was added triethylamine (1.50 ml) and methanesulfonamide (0,70 ml) under ice cooling and the mixture was stirred for 1 h To the reaction solution was added saturated aqueous bicarbonate solution three is under ice cooling and the mixture was extracted with ethyl acetate. The extract was dried over magnesium sulfate, concentrated and the residue was dissolved in a mixed solvent of N,N-dimethylformamide (5.0 ml) and tetrahydrofuran (4.0 ml). Added meantioned sodium (180 mg) and the mixture was stirred at room temperature for 1 h To the reaction mixture were added saturated aqueous sodium hydrogen carbonate solution under ice cooling and the mixture was extracted with ethyl acetate. The extract was dried over magnesium sulfate and concentrated. The residue was separated and purified by chromatography on a column of silica gel (eluent: ethyl acetate:methanol=100:0→ethyl acetate:methanol=90:10) to obtain the specified title compound (123 mg).

1H-NMR (CDCl3) δ: 2,02 (3H, c), 2,66-by 2.73 (2H, m), 3,74-of 3.78 (2H, m), 3,98-4,01 (2H, m), 4,55-4,58(2H, m), of 6.66 (1H, d, J=3 Hz), 7,07-7,63 (6H, m), 7,88(1H, user. c)8,02 (1H, c), 8,55 (1H, c), a total of 8.74(1H, c).

(ii) Obtaining N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5-{2-[2-(methylsulphonyl)ethoxy]ethyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

N-{3-Chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5-{2-[2-(methylthio)ethoxy]ethyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine (70.0 mg) was dissolved in dichloromethane (5.0 ml), was added tetraisopropoxide titanium (0.10 ml), methanol (0,50 ml) and 70% aqueous solution of tert-butylhydroperoxide (8.0 ml) and the mixture was stirred at room temperature for 1 h was Added to the reaction mixture saturated aqueous sodium thiosulfate solution under ice cooling, the mixture re exively at room temperature for 1 h and was extracted with dichloromethane. The extract was dried over magnesium sulfate, concentrated, the residue was separated and purified by chromatography on a column of silica gel (eluent: ethyl acetate:methanol=100:0→ethyl acetate:methanol=90:10). Crystallization from a mixture of diethyl ether-ethyl acetate-hexane gave specified in the header connection (62.5 mg).

1H-NMR (CDCl3) δ: 2,62 (3H, c), 4,57-br4.61 (2H, m), of 6.68 (1H, d, J=3 Hz), 4,16 (1H, m)5,08 (2H, c), of 5.55 (2H, c), 6,33 (1H, user. c), of 6.66 (1H, d, J=3 Hz), 7,09-of 7.60 (7H, m), 7,86 (1H, d, J=3 Hz), 8,11 (1H, c), 8,55 (1H, c).

Example 173

Obtain hydrochloride of N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5-{2-[2-(2,2,2-triptoreline)ethoxy]ethyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

Specified in the title compound (107 mg) was obtained as crystals by the interaction analogous to the methods of example 172 (i)using the compound (200 mg) of example 147, 2,2,2-trifenatate sodium (1.20 g), tetrahydrofuran (7.0 ml) and N,N-dimethylformamide (10 ml) at a reaction temperature of 50°C, and crystallization from a mixture of 4h. an ethyl acetate solution of hydrochloric acid-hexane.

1H-NMR (DMSO-d6) δ: 3,09 (4H, m), 3,30-3,39 (2H, m), br4.61 (2H, user. c)5,12 (2H, user. c)6,53 (1H, d, J=3 Hz), 7,20-8,56 (10H, m).

Example 174

Getting 2-(methylsulphonyl)ethyl{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}carbamate

The dihydrochloride of 5-(2-amino is Teal)-N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine (64,1 mg) and triethylamine (1.0 ml) was dissolved in dichloromethane (5.0 ml), was added 1-({[2-(methylsulphonyl)ethoxy]carbonyl}oxy)pyrrolidine-2,5-dione (45,6 mg) and the mixture was stirred at room temperature for 2 hours was Added to the reaction mixture under ice cooling a saturated aqueous solution of sodium bicarbonate and the mixture was extracted with ethyl acetate. The extract was dried over magnesium sulfate, concentrated, the residue was separated and purified by chromatography on a column of silica gel (eluent: ethyl acetate:methanol=100:0→ethyl acetate:methanol=95:5). Crystallization from a mixture of diethyl ether-hexane gave specified in the header connection (61,0 mg).

1H-NMR (CDCl3) δ: 3,10 (3H, c), 3,48-to 3.52 (2H, m), 3,70 of 3.75 (2H, m), 4,62-and 4.68 (2H, m), 4.75 V-4,79 (2H, m), to 5.57 (1H, m), is 6.78 (1H, d, J=3 Hz), 7,22-to 7.61 (6H, m), 7,92 (1H, m), 8,11 (1H, m), to 8.20 (1H, c), 8,68 (1H, c).

Example 175

Obtain N-{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}-N'-[2-(methylsulphonyl)ethyl]urea

The dihydrochloride of 5-(2-amino-ethyl)-N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine (54,1 mg) and triethylamine (0.7 ml) was dissolved in dichloromethane (10 ml)was added 1,1'-carbonylbis(1H-imidazole) and the mixture was stirred at room temperature. After 1 h was added 2-(methylsulphonyl)ethanamine (1.0 ml) and the mixture was additionally stirred for 1 h was Added to the reaction mixture, a saturated aqueous solution of sodium bicarbonate is ri ice cooling and the mixture was extracted with dichloromethane. The extract was dried over magnesium sulfate, concentrated and the residue was separated, purified by chromatography on a column of silica gel (eluent: ethyl acetate:methanol=100:0→ethyl acetate:methanol=90:10) and was led from a mixture of diethyl ether-ethyl acetate-hexane to obtain specified in the connection header (37.6 mg).

1H-NMR (CDCl3) δ: 2,84 (3H, c), 3,11-3,17 (2H, m), 3,40-3,50 (2H, m), 3,66-and 3.72 (2H, m), 4,39-of 4.44 (2H, m), of 5.55 (2H, m), 6,47 (1H, d, J=3 Hz), 7,00-7,39 (6H, m), 7,81-7,88 (1H, m), to 7.99 (1H, m), 8,40 (1H, c), 8,73 (1H c).

Example 176

Obtain 5-{2-[2-(tert-butylsulfonyl)ethoxy]ethyl}-N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

(i) Obtain 5-{2-[2-(tert-butylthio)ethoxy]ethyl}-N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

2-{2-[4-({3-Chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethoxy}ethanol (150 mg) was dissolved in tetrahydrofuran (6.0 ml), was added triethylamine (1,00 ml) and methanesulfonamide (0,59 ml) under ice cooling and the mixture was stirred for 1 h was Added to the obtained reaction solution, saturated aqueous sodium hydrogen carbonate solution under ice cooling and the mixture was extracted with ethyl acetate. The extract was dried over magnesium sulfate, concentrated and the residue was dissolved in a mixed solvent of N,N-dimethylformamide (4.0 ml) and tetrahydrofuran (6.0 ml). Doba is Lyali 2-methylpropan-2-tiolet sodium (220 mg) and the mixture was stirred at room temperature for 1 h Was added to the reaction mixture, saturated aqueous sodium hydrogen carbonate solution under ice cooling and the mixture was extracted with ethyl acetate. The extract was dried over magnesium sulfate and concentrated. The residue was separated and purified by chromatography on a column of silica gel (eluent: ethyl acetate:methanol=100:0→ethyl acetate:methanol=90:10) to obtain the specified title compound (143 mg).

1H-NMR (CDCl3) δ: of 1.23 (9H, c), 2,69-by 2.73 (2H, m), of 3.73-of 3.78 (2H, m), 3,97-3,99 (2H, m), 4,54-of 4.57 (2H, m), of 6.66 (1H, d, J=3 Hz), 7,07 was 7.45 (6H, m), of 7.64-7.68 per (1H, m), 7,89 (1H, d, J=3 Hz), 8,55 (1H, c), 8,77 (1H, c).

(ii) Obtain 5-{2-[2-(tert-butylsulfonyl)ethoxy]ethyl}-N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

5-{2-[2-(Tert-butylthio)ethoxy]ethyl}-N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine (140 mg) was dissolved in dichloromethane (5.0 ml), was added tetraisopropoxide titanium (0,90 ml), methanol (0,20 ml) and 70% aqueous tert-butylhydroperoxide (7.0 ml) and the mixture was stirred at room temperature for 1 h was Added to the reaction mixture saturated aqueous sodium thiosulfate solution under ice cooling, and the mixture was stirred at room temperature for 1 h and was extracted with dichloromethane. The extract was dried over magnesium sulfate, concentrated, the residue was separated and purified by chromatography on a column of silica gel (eluent: ethyl acetate:methanol=100:0→e is ylacetic:methanol=90:10). Crystallization from a mixture of diethyl ether-ethyl acetate-hexane gave specified in the header of the connection a (10.6 mg).

1H-NMR (CDCl3) δ: 1,24 (9H, c), 3,00 totaling 3.04 (2H, m), 3,97-4,08 (4H, m), 4,49-to 4.52 (2H, m), 6,59 (1H, d, J=3 Hz), 7,00-7,56 (7H, m), to 7.84 (1H, d, J=3 Hz), of 8.27 (1H, c), 8,48 (1H, c).

Melting point: 79,5-81,5°C.

Example 177

Obtain N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5-{2-[2-(phenylsulfonyl)ethoxy]ethyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

(i) Obtaining N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5-{2-[2-(phenylthio)ethoxy]ethyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

Specified in the header connection (96,4 mg) was obtained by interaction of a similar method in example 172 (i)using the compound (100 mg) of example 147, benzothioate sodium (200 mg), tetrahydrofuran (5.0 ml) and N,N-dimethylformamide (4.0 ml).

1H-NMR (CDCl3) δ: 3,06-3,10 (2H, m), 3.75 to with 3.79 (2H, m), 3,94-of 3.97 (2H, m), to 4.52-4,55 (2H, m), of 6.66 (1H, d, J=3 Hz), 7,01-7,56 (12H, m), 7,88 (1H, d, J=3 Hz), 8,56(1H, c), 8,71 (1H, c).

(ii) Obtaining N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5-{2-[2-(phenylsulfonyl)ethoxy]ethyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

Specified in the title compound (7.2 mg) was obtained by interaction of a similar method in example 172 (ii)using N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5-{2-[2-(phenylthio)ethoxy]ethyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine (60 mg), dichloromethane (5.0 ml), N,N-dimethylformamide (2.0 ml), t is triisopropoxide titanium (0,90 ml), methanol (0,20 ml) and 70% aqueous tert-butylhydroperoxide (4,0 ml).

1H-NMR (CDCl3) δ: 3,23-of 3.27 (2H, m), 3,88-4,00 (4H, m), 4,42 is 4.45 (2H, m), to 6.58 (1H, d, J=3 Hz), 7,00-7,70 (12H, m), 7,79 (1H, d, J=3 Hz), 8,13 (1H, c), of 8.47 (1H, c).

Example 178

Getting 2-[(2-{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethoxy}ethyl)sulfinil]ethanol

The compound (120 mg)obtained by the interaction analogous to the methods of example 172 (i)using the compound (200 mg) of example 147, 2-hydroxyacetate sodium (2,02 g), tetrahydrofuran (6.0 ml) and N,N-dimethylformamide (5.0 ml), was dissolved in dichloromethane (7.0 ml). Added m-chloroperbenzoic acid (110 mg) at -18°C and the mixture was stirred for 5 hours To the reaction mixture were added saturated aqueous sodium hydrogen carbonate solution under ice cooling and the mixture was extracted with dichloromethane. The extract was dried over magnesium sulfate, concentrated, the residue was separated and purified by chromatography on a column of silica gel (eluent: ethyl acetate:methanol=100:0→ethyl acetate:methanol=80:20). Crystallization from a mixture of diethyl ether-ethyl acetate-hexane gave specified in the header connection (97,0 mg).

1H-NMR (CDCl3) δ: 2,66-by 2.73 (2H, m), 2,90 are 2.98 (2H, m), 3,93 is 4.13 (6H, m), 4,56-to 4.62 (2H, m), of 6.68 (1H, d, J=3 Hz), 7,08-to 7.59 (7H,m), 7,83 (1H, d, J=3 Hz), of 8.37 (1H, m), 8,55 (1H, c).

Example 179

Getting 2-[(2-{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethoxy}ethyl)sulfonyl]ethanol

Specified in the header connection (60,2 mg) was obtained as crystals by the interaction analogous to the methods of example 172 (ii), using compound (a 87.0 mg) of example 178, dichloromethane (4.0 ml), N,N-dimethylformamide (2.0 ml), tetraisopropoxide titanium (0,90 ml), methanol (0,50 ml) and 70% aqueous tert-butylhydroperoxide (5.0 ml).

1H-NMR (CDCl3) δ: 2,78-2,82 (2H, m), 3,34-to 3.38 (2H, m), with 3.79 (2H, m), a 4.03-4,13 (4H, m), 4,57-4,60 (2H, m), of 6.68 (1H, d, J=3 Hz), 7,07-EUR 7.57 (7H, m), 7,80 (1H, d, J=3 Hz), 8,23 (1H, m), 8,54 (1H, c).

Example 180

Obtain N-{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}-1-(methylsulphonyl)methanesulfonamide

The dihydrochloride of 5-(2-amino-ethyl)-N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine (245 mg) and N-methylmorpholine (1.0 ml) was dissolved in dichloromethane (6.0 ml), (methylsulphonyl)methanesulfonanilide (0,40 ml) was added dropwise under ice cooling and the mixture was stirred for 1 h Saturated aqueous solution of sodium bicarbonate was added under ice cooling and the mixture was extracted with dichloromethane. The extract was dried over magnesium sulfate, concentrated, the residue was separated and purified by chromatography on a column of silica gel (eluent: ethyl shall zitat:methanol=100:0→ethyl acetate:methanol=80:20). Crystallization from a mixture of diethyl ether-ethyl acetate gave specified in the header connection (79,4 mg) as crystals.

1H-NMR (CDCl3) δ: of 3.60 (3H, user. c), 3,83-to 3.92 (4H, m), 4,82 (2H, user. c)of 6.68 (1H, d, J=3 Hz), 7.24 to 7,99 (8H, m), 8,73 (1H, c), 8,73 (1H, c), 9,72 (1H, c).

Example 181

Getting hydrochloride 3-[2-chloro-4-(6,7-dihydro-9H-pyrimido[4',5':4,5]pyrrolo[2,1-c][1,4]oxazin-4-ylamino)phenoxy]benzonitrile

(i) Obtaining 4-phenoxy-6,7-dihydro-9H-pyrimido[4',5':4,5]pyrrolo[2,1-c][1,4]oxazine

Compound (130 mg)obtained in example 21 (ii)was dissolved in N,N-dimethylformamide (2,16 ml) and sequentially added cesium carbonate (1,05 g) and 1,2-dibromethane (0,255 ml). The mixture was stirred at room temperature for 16 hours, the Reaction mixture was diluted with ethyl acetate (30 ml) and washed with water (20 ml). The organic layer was separated, dried over magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in N,N-dimethylformamide (1.08 ml)was added tert-piperonyl potassium (90,5 mg) and the mixture was stirred at room temperature for 1 h was Added a mixture of ethyl acetate (30 ml)-water (20 ml), the organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (hexane/ethyl acetate=70/30→0/100) to obtain the specified title compound (76 mg).

1H-NMR (DCl 3) δ 4,20 (2H, t, J=5 Hz), 4,55 (2H, t, J=5 Hz), is 5.06 (2H, c), 6,40 (1H, c), a 7.2 to 7.5 (5H, m), 8,44 (1H, c).

(ii) obtaining the hydrochloride of 3-[2-chloro-4-(6,7-dihydro-9H-pyrimido[4',5':4,5]pyrrolo[2,1-c][1,4]oxazin-4-ylamino)phenoxy]benzonitrile

A mixture of 4-phenoxy-6,7-dihydro-9H-pyrimido[4',5':4,5]pyrrolo[2,1-c][1,4]oxazine (69 mg), 3-(4-amino-2-chlorophenoxy)benzonitrile (95 mg), pyridine hydrochloride (75 mg) and 1-methyl-2-pyrrolidone (1 ml) was stirred at 140°C for 14 hours after the reaction mixture was diluted with ethyl acetate and washed with saturated aqueous sodium hydrogen carbonate solution and saturated salt solution. The organic layer was dried over magnesium sulfate. After concentration under reduced pressure the residue was subjected to chromatography on a column of silica gel (hexane/ethyl acetate=50/50→0/100). The obtained fractions were collected, concentrated, the residue was dissolved in ethyl acetate (2 ml) and treated with a mixture of 4h. hydrochloric acid-ethyl acetate (0,13 ml) to obtain the specified title compound (81 mg) as crystals of the hydrochloride.

1H-NMR (DMSO-d6) δ to 4.17 (2H, t, J=5 Hz), and 4.75 (2H, m), 5,07 (2H, c), 6,55 (1H, c), of 7.2 to 7.7 (6H, m), 7,94 (1H, m), to 8.70 (1H, c), to 9.91 (1H, user. c).

Example 182

Obtain N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5-(2-{[2-(methylsulphonyl)ethyl]amino}ethyl)-5H-pyrrolo[3,2-d]pyrimidine-4-amine

(i) Obtaining 4-chloro-5-(2,2-diatexite)-5H-pyrrolo[3,2-d]pyrim the Dean

4-Chloro-5H-pyrrolo[3,2-d]pyrimidine (1 g) was dissolved in N,N-dimethylformamide (13 ml)was sequentially added cesium carbonate (6,37 g) and 2-bromo-1,1-diethoxyethane (2,94 ml) and the mixture was stirred at 80°C for 4.5 h, the Reaction mixture was diluted with ethyl acetate (100 ml) and washed with water (80 ml). The organic layer was separated, dried over magnesium sulfate and evaporated under reduced pressure. The residue was purified by chromatography on a column of silica gel (hexane/ethyl acetate=50/50→0/100) to obtain the specified title compound (1.26 g) as a yellow oil.

1H-NMR (CDCl3) δ 1.14 in (6H, t, J=6 Hz), 3,40 (2H, m), and 3.72 (2H, m), 4,08 (1H, m), 4,56 (2H, d, J=5 Hz), of 6.71 (1H, d, J=3 Hz), 7,55 (1H, d, J=3 Hz), 8,69 (1H, c).

(ii) Obtaining 4-phenoxy-5-(2,2-diatexite)-5H-pyrrolo[3,2-d]pyrimidine

A mixture of 4-chloro-5-(2,2-diatexite)-5H-pyrrolo[3,2-d]pyrimidine (1 g), phenol (420 mg), potassium carbonate (617 mg) and 1-methyl-2-pyrrolidone (6,74 ml) was stirred under heating at 140°C for 6 hours, the Reaction mixture was diluted with ethyl acetate (100 ml) and washed with water (80 ml). The organic layer was separated, dried over magnesium sulfate and evaporated under reduced pressure. The residue was purified by chromatography on a column of silica gel (hexane/ethyl acetate=90/10→40/60) to obtain specified in the connection header (1,15 g) as a yellow oil.

1H-NMR (CDCl3) δ of 1.13 (6H, t, J=7 Hz), 3,40 (2H, m), of 3.69 (2H, m), 4,51 (2H, d, J=6 Hz), was 4.76 (1H, t, J=6 Hz), of 6.65 (1H, d, J= Hz), a 7.2 to 7.5 (6H, m), to 8.45 (1H, c).

(iii) Obtaining 2-(4-phenoxy-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethane-1,1-diol

4 Phenoxy-5-(2,2-diatexite)-5H-pyrrolo[3,2-d]pyrimidine (1.1 g) was dissolved in a mixture of dichloromethane (4,53 ml)-triperoxonane acid (4,53 ml) and the mixture was stirred at room temperature for 16 hours the Reaction mixture was concentrated under reduced pressure and the residue was dissolved in ethyl acetate (100 ml). The mixture was washed with a saturated aqueous solution of sodium bicarbonate (80 ml), the organic layer was dried over magnesium sulfate and concentrated under reduced pressure to obtain specified in the title compound (826 mg) as a white solid.

1H-NMR (DMSO-d6) δ of 4.35 (2H, d, J=6 Hz), to 5.17 (1H, t, J=6 Hz), 6,14 (2H, d, J=6 Hz), 6,59 (1H, d, J=3 Hz), 7,2-7,6 (5H, m), of 7.75 (1H, d, J=3 Hz), of 8.28 (1H, c).

(iv) Obtaining 2-(methylsulphonyl)-N-[2-(4-phenoxy-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethyl]ethanamine

2-(4-Phenoxy-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethane-1,1-diol (500 mg) and 2-(methylsulphonyl)ethylamine (341 mg) was dissolved in a mixture of N,N-dimethylformamide (29 ml)-acetic acid (2.9 ml) and the mixture was stirred at room temperature for 1.5 hours was Added triacetoxyborohydride sodium (579 mg) and the mixture was stirred at room temperature for 16 hours the Reaction mixture was concentrated under reduced pressure and the residue was purified by chromatography on a column with silica gel (ethyl acetate/methane is l=100/0→70/30) to obtain the specified title compound (508 mg) in the form of like candied substances.

1H-NMR (CDCl3) δ 2,84 (3H, c), to 3.0-3.2 (6H, m), of 4.54 (2H, t, J=6 Hz), of 6.66 (1H, d, J=3 Hz), 7,2-7,5 (6H, m), to 8.45 (1H, c).

(v) Obtaining N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5-(2-{[2-(methylsulphonyl)ethyl]amino}ethyl)-5H-pyrrolo[3,2-d]pyrimidine-4-amine

2-(Methylsulphonyl)-N-[2-(4-phenoxy-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethyl]ethanamine (500 mg) was dissolved in tetrahydrofuran (5 ml), was added di-tert-BUTYLCARBAMATE (0,478 ml) and triethylamine (0,29 ml) and the mixture was stirred at room temperature for 3 hours the Reaction mixture was concentrated under reduced pressure and the residue was purified by chromatography on a column of silica gel (hexane/ethyl acetate=80/20 → 0/100). A mixture of part (243 mg), taken from the obtained residue (491 mg), 3-chloro-4-[3-(trifluoromethyl)phenoxy]aniline (228 mg), pyridine hydrochloride (183 mg) and phenol (406 mg) was stirred at 140°C for 14 hours after the reaction mixture was diluted with dichloromethane (50 ml) and washed with saturated aqueous sodium hydrogen carbonate (30 ml). The organic layer was dried over magnesium sulfate. After concentration under reduced pressure the residue was subjected to chromatography on a column of silica gel (ethyl acetate/methanol=100/0→70/30) and was led from diisopropyl ether to obtain specified in the title compound (123 mg).

1H-NMR (DMSO-d6) δ is 2.88 (3H, c), 2,89 (2H, m), 2,99 (2H, m), and 3.16 (2H, t, J=6 Hz), 4,50 (2H, m), 6,51 (1H, d, J=3 Hz), 7,22 (2H, m), 7,31 (1H, d, J=9 is C), 7,46 (1H, d, J=8 Hz), of 7.5 to 7.7 (3H, m), of 8.04 (1H, d, J=2 Hz), 8,35 (1H, c).

Example 183

Obtain 2-[2-(4-{[4-[(6-methylpyridin-3-yl)oxy]-3-(trifluoromethyl)phenyl]amino}-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethoxy]ethanol

A mixture of 2-[2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethoxy]ethylbenzoic (150 mg), 4-[(6-methylpyridin-3-yl)oxy]-3-(trifluoromethyl)aniline (175 mg) and 1-methyl-2-pyrrolidone (0,863 ml) was stirred under heating at 140°C for 2.5 h, the Reaction mixture was diluted with ethyl acetate (80 ml) and washed with an aqueous solution of sodium bicarbonate (30 ml). The organic layer was separated, dried over magnesium sulfate and evaporated under reduced pressure. The residue was purified by chromatography on a column of silica gel (ethyl acetate/methanol=100/0→90/10). The target fraction was concentrated under reduced pressure. The obtained residue was dissolved in methanol (1.9 ml)was added 1N. sodium hydroxide (0,433 ml) and the mixture was stirred at room temperature for 1.5 hours was Added 1N. hydrochloric acid (0,433 ml), the mixture was diluted with ethyl acetate (80 ml) and washed with saturated salt solution (30 ml). The organic layer was dried over magnesium sulfate. After concentration under reduced pressure the residue was subjected to chromatography on a column of silica gel (ethyl acetate/methanol=100/0→90/10) and was led from diisopropyl ether to obtain specified in sagola the ke of the compound (118 mg).

1H-NMR (DMSO-d6) δ of 2.46 (3H, c), 3,47 (4H, user. c), 3,82 (2H, m), of 4.66 (3H, m), 6,51 (1H, d, J=3 Hz), 7,10 (1H, d, J=9 Hz), 7,31 (2H, m), 7,68 (1H, d, J=3 Hz), of 7.90 (1H, DD, J=3 Hz, 9 Hz), 8,10 (1H, d, J=3 Hz), 8,24 (1H, d, J=3 Hz), 8.30 to (1H, c), 8,99 (1H, user. c).

Example 184

Obtaining 2-(4-{[3-chloro-4-(3-chlorophenoxy)phenyl]amino}-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethanol

Specified in the title compound (81 mg) was obtained as colorless crystals by the interaction is similar to the method of example 183 using 2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethylbenzoic (100 mg), 3-chloro-4-(3-chlorophenoxy)aniline (126 mg) and 1-methyl-2-pyrrolidone (0,66 ml).

1H-NMR (DMSO-d6) δ a 3.87 (2H, m), a 4.53 (2H, t, J=4.5 Hz), of 6.31 (1H, user. c)6,51 (1H, d, J=3 Hz), to 6.88 (1H, d, J=9 Hz), to 6.95 (1H, c), to 7.15 (1H, d, J=9 Hz), 7,28 (1H, d, J=9 Hz), 7,38 (1H, t, J=9 Hz), 7,60 (1H, DD, J=2 Hz, 9 Hz), 7,66 (1H, d, J=3 Hz), of 7.97 (1H, d, J=2 Hz), a 8.34 (1H, c), of 9.89 (1H, user. c).

Example 185

Getting 2-{2-[4-({3-methoxy-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethoxy}ethanol

Specified in the title compound (80 mg) was obtained as colorless crystals by the interaction is similar to the method of example 183 using 2-[2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethoxy]ethylbenzoic (150 mg), 3-methoxy-4-[3-(trifluoromethyl)phenoxy]aniline (185 mg) and 1-methyl-2-pyrrolidone (0,863 ml).

1H-NMR (DMSO-d6) δ to 3.52 (4H, m), 3,74 (3H,c), of 3.85 (2H, t, J=5 Hz)and 4.65 (2H, t, J=5 Hz), was 4.76 (1H, t, J=5 Hz), 6,51 (1H, d, J=3 Hz), 7,13 (3H, m), 7,35 (2H, m), 7,49 (1H, d, J=2 Hz), 7,55 (1H, t, J=8 Hz), to 7.68 (1H, d, J=3 Hz), 8,32 (1H, c), of 8.90 (1H, user. c).

Example 186

Getting 2-{2-[4-({3-(hydroxymethyl)-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethoxy}ethanol

Specified in the title compound (175 mg) was obtained as colorless crystals by the interaction is similar to the method of example 183 using 2-[2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethoxy]ethylbenzoic (150 mg), {5-amino-2-[3-(trifluoromethyl)phenoxy]phenyl}methanol (184 mg) and 1-methyl-2-pyrrolidone (0,863 ml).

1H-NMR (DMSO-d6) δ to 3.52 (4H, m), 3,74 (3H, c), 3,85 (2H, t, J=5 Hz)and 4.65 (2H, t, J=5 Hz), was 4.76 (1H, t, J=5 Hz), 6,51 (1H, d, J=3 Hz), 7,13 (3H, m), 7,35 (2H, m), 7,49 (1H, d, J=2 Hz), 7,55 (1H, t, J=8 Hz,), to 7.68 (1H, d, J=3 Hz), 8,32 (1H, c), of 8.90 (1H, user. c).

Example 187

Getting 2-{2-[4-({3-methyl-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethoxy}ethanol

Specified in the title compound (98 mg) was obtained as colorless crystals by the interaction is similar to the method of example 183 using 2-[2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethoxy]ethylbenzoic (150 mg), 3-methyl-4-[3-(trifluoromethyl)phenoxy]aniline (174 mg) and 1-methyl-2-pyrrolidone (0,863 ml).

1H-NMR (DMSO-d6) δ a 2.13 (3H, c), 3,51 (4H, m), a-3.84 (2H, t, J=4.5 Hz), 4,63 (2H, t, J=4,5 is C), 4,74 (1H, t, J=4.5 Hz), of 6.49 (1H, d, J=3 Hz),? 7.04 baby mortality (1H, d, J=9 Hz), 7,16 (2H, m), 7,41 (1H, d, J=8 Hz), of 7.5 to 7.7 (4H, m), 8,29 (1H, c), 8,83 (1H, user. c).

Example 188

Getting 2-(methylsulphonyl)-N-{2-[4-({3-methyl-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}ndimethylacetamide

(i) Obtain tert-butyl{2-[4-({3-methyl-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}carbamate

A mixture of tert-butyl[2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethyl]carbamate (297 mg), 3-methyl-4-[3-(trifluoromethyl)phenoxy]aniline (401 mg) and isopropyl alcohol (2,97 ml) was stirred at 80°C for 16 hours, the Reaction mixture was diluted with ethyl acetate (80 ml) and washed with an aqueous solution of sodium bicarbonate (30 ml). The organic layer was separated, dried over magnesium sulfate and evaporated under reduced pressure. The residue was purified by chromatography on a column of silica gel (hexane/ethyl acetate=90/10→0/100) to obtain the specified title compound (528 mg) as a white powder.

1H-NMR (CDCl3) δ of 1.47 (9H, c), of 2.21 (3H, c), a 3.50 (2H, m), 4,46 (2H, m), 5,11 (1H, m), to 6.58 (1H, d, J=3 Hz), 6,97 (1H, d, J=9 Hz), 7,0-7,2 (3H, m), 7,27 (1H, m), 7,39 (1H, t, J=8 Hz), 7,69 (2H, m), to 8.45 (1H, user. c), and 8.50 (1H, c).

(ii) Obtaining 5-(2-amino-ethyl)-N-{3-methyl-4-[3-(trifluoromethyl)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

tert-Butyl{2-[4-({3-methyl-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}carbamate (494 is g) was dissolved in dichloromethane (6.4 ml), added triperoxonane acid (4.8 ml) and the mixture was stirred at room temperature for 1 h the Reaction mixture was concentrated under reduced pressure, the residue was diluted with ethyl acetate (50 ml) and washed with an aqueous solution of sodium bicarbonate (30 ml). The organic layer was separated, dried over magnesium sulfate and concentrated under reduced pressure to obtain specified in the title compound (442 mg) in powder form.

1H-NMR (CDCl3) δ of 2.20 (3H, c), 3,30 (2H, t, J=5 Hz), to 4.46 (2H, t, J=5 Hz), is 6.61 (1H, d, J=3 Hz), to 6.95 (1H, d, J=9 Hz), 7,0-7,5 (6H, m), 7,51 (1H, d, J=3 Hz)and 8.50 (1H, c).

(iii) Obtaining 2-(methylsulphonyl)-N-{2-[4-({3-methyl-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}ndimethylacetamide

Specified in the title compound (89 mg) was obtained as colorless powder crystals by the interaction is similar to the method of example 155 (iv)using 5-(2-amino-ethyl)-N-{3-methyl-4-[3-(trifluoromethyl)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine (196 mg), 2-(methylsulphonyl)acetic acid (64 mg), hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (133 mg), monohydrate of 1-hydroxybenzotriazole (94 mg), triethylamine (0,319 ml) and N,N-dimethylformamide (5.0 ml).

1H-NMR (DMSO-d6) δ and 2.14 (3H, c)to 3.09 (3H, c), of 3.45 (2H, m), of 4.05 (2H, c), 4,56 (2H, t, J=7 Hz), 6,47 (1H, d, J=3 Hz),? 7.04 baby mortality (1H, d, J=9 Hz), 7,17 (2H, m), 7,47 (1H, m), to 7.59 (4H, m), 8,29 (1H, c), 8,55 (1H, user. c)8,67 (1H, t, J=5,5 Hz).

Example 189

Getting 2-{2-[4-({3-methyl-4-[3-(triptoreline)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethoxy}ethanol

Specified in the title compound (128 mg) was obtained as colorless crystals by the interaction is similar to the method of example 183 using 2-[2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethoxy]ethylbenzoic (150 mg), 3-methyl-4-[3-(triptoreline)phenoxy]aniline (184 mg) and 1-methyl-2-pyrrolidone (0,863 ml).

1H-NMR (DMSO-d6) δ 2,12 (3H, c), 3,51 (4H, m), a-3.84 (2H, t, J=5 Hz), 4,63 (2H, t, J=5 Hz), to 4.73 (1H, t, J=5 Hz), of 6.49 (1H, d, J=3 Hz), 6.87 in (2H, m),? 7.04 baby mortality (2H, m), 7,47 (1H, t, J=8 Hz), to 7.59 (2H, m), 7,66 (1H, d, J=3 Hz), 8,29 (1H, c), 8,82 (1H, user. c).

Example 190

Getting 2-(methylsulphonyl)-N-{2-[4-({3-methyl-4-[3-(triptoreline)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}ndimethylacetamide

(i) Obtain tert-butyl{2-[4-({3-methyl-4-[3-(triptoreline)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}carbamate

tert-Butyl[2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethyl]carbamate (297 mg) and 3-methyl-4-[3-(triptoreline)phenoxy]aniline (425 mg) was dissolved in isopropyl alcohol (2,97 ml) and the mixture was stirred at 80°C for 16 hours After cooling to room temperature the mixture was diluted with ethyl acetate (60 ml) and washed with an aqueous solution of sodium bicarbonate (30 ml). The organic layer was dried over sulfate mage the Oia and concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel (eluent: hexane:ethyl acetate=80:20→0:100) to obtain the specified title compound (563 mg) as a white powder.

1H-NMR (CDCl3) δ of 1.47 (9H, c), of 2.20 (3H, c), 3,49 (2H, m), 4,46 (2H, m)5,08 (1H, m), 6,59 (1H, d, J=3 Hz), 6,78 (1H, m)6,86 (2H, m), 6,97 (1H, m), 7,16 (1H, d, J=3 Hz), 7,27 (2H, m), 7,69 (2H, m), 8,43 (1H, user. c), and 8.50 (1H, c).

(ii) Obtaining 5-(2-amino-ethyl)-N-{3-methyl-4-[3-(triptoreline)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

tert-Butyl{2-[4-({3-methyl-4-[3-(triptoreline)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}carbamate (523 mg) was dissolved in dichloromethane (6.4 ml)was added triperoxonane acid (4.8 ml) and the mixture was stirred at room temperature for 2 hours the Reaction mixture was concentrated under reduced pressure and the residue was diluted with ethyl acetate (50 ml) and washed with an aqueous solution of sodium bicarbonate (40 ml). The organic layer was separated, dried over magnesium sulfate and concentrated under reduced pressure to obtain specified in the title compound (420 mg) as a white powder.

1H-NMR (CDCl3) δ of 2.20 (3H, c), 3,30 (2H, t, J=4.5 Hz), to 4.46 (2H, t, J=4.5 Hz), 6,62 (1H, d, J=3 Hz), 6,85 (3H, m), of 6.96 (1H, d, J=9 Hz), 7,19 (1H, d, J=3 Hz), 7,27 (1H, m), 7,44 (1H, DD, J=2 Hz, 9 Hz), 7,50 (1H, d, J=3 Hz)and 8.50 (1H, c).

(iii) Obtaining 2-(methylsulphonyl)-N-{2-[4-({3-methyl-4-[3-(triptoreline)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethyl}azeta the IDA

A solution of 5-(2-amino-ethyl)-N-{3-methyl-4-[3-(triptoreline)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine (174 mg), 2-(methylsulphonyl)acetic acid (54 mg), hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (112 mg), monohydrate of 1-hydroxybenzotriazole (79 mg) and triethylamine (0,273 ml) in N,N-dimethylformamide (7,69 ml) was stirred at room temperature for 16 hours, the Reaction mixture was diluted with ethyl acetate (80 ml) and washed with water (60 ml). The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was subjected to chromatography on a column of silica gel (eluent: ethyl acetate:methanol=100:0 → 92:8) and was led from diisopropyl ether to obtain specified in the title compound (92 mg) as colorless crystals.

1H-NMR (DMSO-d6) δ and 2.14 (3H, c), 3,10 (3H, c), of 3.46 (2H, q, J=6 Hz), 4,06 (2H, c), 4,56 (2H, t, J=6 Hz), 6.48 in (1H, d, J=3 Hz), 6.89 in (2H, m), 7,06 (2H, m), of 7.48 (1H, t, J=8 Hz), to 7.59 (3H, m), 8,30 (1H, c), 8,55 (1H, user. c)8,67 (1H, t, J=6 Hz).

Melting point: 106-108°C.

Example 191

Obtaining N-[2-(4-{[3-chloro-4-(3-chlorophenoxy)phenyl]amino}-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethyl]-2-(methylsulphonyl)ndimethylacetamide

(i) Obtaining tert-butyl-2-(4-{[3-chloro-4-(3-chlorophenoxy)phenyl)amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethylcarbamate

A mixture of tert-butyl 2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethylcarbamate (1.19 g), 3-chloro-4-(3-CHL is Hinoki)aniline (1.22 g) and isopropyl alcohol (12.0 ml) was stirred at 80°C for 15 hours Under ice cooling was added an aqueous solution of sodium bicarbonate and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated salt solution and dried over anhydrous magnesium sulfate. The solvent was concentrated under reduced pressure, the residue was purified by chromatography on silica gel (eluent: hexane/ethyl acetate=50/50→100/0) and washed with a mixture of diisopropyl ether-hexane to obtain specified in the connection header (1,69 g) in the form of crystals.

1H-NMR (CDCl3) δ: 1.50 in (9H, c), 3,4-3,6 (2H, m), 4,4-4,6 (2H, m), a 5.0 to 5.1 (1H, m), is 6.61 (1H, d, J=2.6 Hz), 6,85-7,05 (2H, m), 7,07 (2H, d, J=8,8 Hz), 7,18 (1H, d, J=2.6 Hz), 7,2-7,3 (1H, m), a 7.85-of 7.95 (1H, m), 8,0-with 8.05 (1H, m), charged 8.52 (1H, c), to 8.62 (1H, user. c).

(ii) Obtaining dihydrochloride 5-(2-amino-ethyl)-N-[3-chloro-4-(3-chlorophenoxy)phenyl]-5H-pyrrolo[3,2-d]pyrimidine-4-amine

To a solution of tert-butyl 2-(4-{[3-chloro-4-(3-chlorophenoxy)phenyl]amino}-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethylcarbamate (1,69 g) in tetrahydrofuran (32 ml) was added 2n. hydrochloric acid (16 ml). The reaction mixture was stirred at 65°C for 18 h and concentrated. Was added ethanol and the mixture is again concentrated. To the residue was added ethyl acetate and diisopropyl ether, the precipitate was separated by filtration and washed with diisopropyl ether to obtain specified in the title compound (1.50 g) in the form of crystals.

1H-NMR (DMSO-d6+CDCl3) δ: 3,3-3,6 (4H, m), 5,0-of 5.15 (2H, m), of 6.71 (1, d, J=3.2 Hz), the 6.9 to 7.0 (2H, m), 7,1-7,2 (1H, m), 7,22 (1H, d, J=8,8 Hz), 7,3 was 7.45 (1H, m), and 7.6 to 7.7 (1H, m), 7,87 (1H, d, J=2.6 Hz), with 8.05 (1H, d, J=2.4 Hz), 8,2-8,4 (2H, m), 8,71 (1H, c).

(iii) Obtaining N-[2-(4-{[3-chloro-4-(3-chlorophenoxy)phenyl]amino}-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethyl]-2-(methylsulphonyl)ndimethylacetamide

To a solution of dihydrochloride of 5-(2-amino-ethyl)-N-[3-chloro-4-(3-chlorophenoxy)phenyl]-5H-pyrrolo[3,2-d]pyrimidine-4-amine (200 mg), 2-(methylsulphonyl)acetic acid (113 mg) and 1-hydroxybenzotriazole (122 mg) in N,N-dimethylformamide (5.0 ml) solution was added triethylamine (419 mg) in N,N-dimethylformamide (1.25 ml) and the hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (173 mg) under ice cooling. After stirring the reaction mixture at room temperature for 16 h was added water under ice cooling and the mixture was extracted twice with ethyl acetate. The organic layers were collected, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by chromatography on a column of silica gel (eluent: ethyl acetate/methanol=100/0→80/20), and recrystallized from a mixture of ethanol-ethyl acetate-diisopropyl ether to obtain specified in the title compound (151 mg) as crystals.

1H-NMR (CDCl3) δ: 3,13 (3H, c), 3,6-3,8 (2H, m)to 3.99 (2H, c), 4,4-4,6 (2H, m), 6,62 (1H, d, J=3,4 Hz), 6,85-to 6.95 (2H, m), of 7.0, and 7.1 (2H, m), 7,2-7,3 (2H, m), 7,7-7,8 (1H, m), 7.95 is to 8.0 (1H, m), 8,19 (1H, c), charged 8.52 (1H, c).

Melting point: 206-207°C.

Example 192

Getting dihydrochloride of 2-[{3-[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]propyl}(methyl)amino]ethanol

(i) Obtaining 4-chloro-5-(3-chloropropyl)-5H-pyrrolo[3,2-d]pyrimidine

To a solution of 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (1.54 g) in N,N-dimethylformamide (20 ml) was added cesium carbonate (4,89 g) under ice cooling and the mixture was stirred under ice cooling for 20 minutes was Added 1-bromo-3-chloropropane (1.89 g) and the mixture was stirred under ice cooling for 1 h and at room temperature for 32 hours, the Reaction mixture was poured into water (40 ml) and the mixture was extracted with ethyl acetate (60 ml×2). The organic layers were combined, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (eluent: hexane:ethyl acetate=80:20→50:50) to obtain specified in the connection header (1,87 g).

1H-NMR (CDCl3) δ: 2,35 (2H, m), 3,49 (2H, t, J=6.0 Hz), 4,69 (2H, t, J=6.6 Hz), was 6.73 (1H, d, J=3.0 Hz), 7,56 (1H, d, J=3.0 Hz), to 8.70 (1H, c).

(ii) Obtaining N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5-(3-chloropropyl)-5H-pyrrolo[3,2-d]pyrimidine-4-amine

A mixture of 4-chloro-5-(3-chloropropyl)-5H-pyrrolo[3,2-d]pyrimidine (839 mg), 3-chloro-4-[(3-terbisil)oxy]aniline (1.10 g) and isopropyl alcohol (5 ml) was stirred at 80°C for 1.5 h the Mixture was concentrated under reduced pressure, was added to the residue saturated water is a solution of sodium bicarbonate (30 ml) and the mixture was extracted with ethyl acetate (30 ml×3). The organic layers were combined, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (eluent: hexane:ethyl acetate=90:10→20:80) to obtain the specified title compound (1.19 g).

1H-NMR (CDCl3) δ: at 2.36 (2H, m), of 3.56 (2H, t, J=5.7 Hz), 4,47 (2H, t, J=6.9 Hz), 5,14 (2H, c), 6,60 (1H, d, J=3.3 Hz), was 6.73 (1H, user. c)6,94 (1H, d, J=8.7 Hz), 7,02 (1H, m), 7,19-7,40 (5H, m), the 7.65 (1H, d, J=3.3 Hz), 8,49(1H, c).

(iii) obtaining the dihydrochloride of 2-[{3-[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]propyl}(methyl)amino]ethanol

A mixture of N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5-(3-chloropropyl)-5H-pyrrolo[3,2-d]pyrimidine-4-amine (634 mg), 2-methylaminoethanol (534 mg) and N,N-dimethylformamide (5 ml) was stirred at room temperature for 64 hours After concentration under reduced pressure, to the residue was added saturated aqueous sodium hydrogen carbonate solution (10 ml) and the mixture was extracted with ethyl acetate (55 ml×2). The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on a column with a basic silica gel (eluent: hexane:ethyl acetate=80:20→0:100). To the obtained amorphous solid substance was added 4n. an ethyl acetate solution of hydrogen chloride (10 ml) and after concentration under reduced pressure the residue precrystallization is whether from a mixture of ethanol-ethyl acetate to obtain specified in the title compound (523 mg).

1H-NMR (DMSO-d6) δ: 2,16 of-2.32 (2H, m), is 2.74 (3H, c), 2,94 is 3.40 (4H, m), 3,62-of 3.80 (2H, m), 4,74-4,84 (2H, m), 5,31 (2H, c), 6,69 (1H, m), 7,20 (1H, m), 7.29 trend and 7.36 (5H, m), 7,43-to 7.50 (2H, m), 7,71 (1H, m), 8,03 (1H, user. c)8,64 (1H, c), 9,84 (1H, user. c), 10,12 (1H, user. c).

Example 193

Getting dihydrochloride N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5-[3-(dimethylamino)propyl]-5H-pyrrolo[3,2-d]pyrimidine-4-amine

N-{3-Chloro-4-[(3-terbisil)oxy]phenyl}-5-(3-chloropropyl)-5H-pyrrolo[3,2-d]pyrimidine-4-amine (560 mg) was dissolved in 2.0m tertrahydrofuran ring solution of dimethylamine (5 ml) and the mixture was stirred at room temperature for 26 hours was Additionally added 2.0m tertrahydrofuran ring solution of dimethylamine (5 ml) and the mixture was stirred at room temperature for 20 hours was Again added 2.0m tertrahydrofuran ring solution of dimethylamine (10 ml) and the mixture was stirred at room temperature for 24 hours After concentrating the reaction mixture under reduced pressure, to the residue was added saturated aqueous sodium hydrogen carbonate solution (20 ml) and the mixture was extracted with ethyl acetate (35 ml×2). The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on a column with a basic silica gel (eluent: hexane:ethyl acetate=90:10→20:80) and to the resulting amorphous solid substance was added 4n. an ethyl acetate solution is aristovo hydrogen (10 ml). After concentration under reduced pressure the residue was recrystallized from a mixture of ethanol-ethyl acetate to obtain specified in the title compound (428 mg).

1H-NMR (DMSO-d6) δ: 2,18-of 2.26 (2H, m), 2,70 (6H, c), 2,94 totaling 3.04 (2H, m), 4,77-4,84 (2H, m), and 5.30 (2H, c), to 6.67 (1H, m), 7,19 (1H, m), 7,28-7,34 (4H, m), 7,43-7,51 (2H, m), 7,71 (1H, m), of 8.04 (1H, m), 8,63 (1H, c), 9,87 (1H user. c)a 10.74 (1H, user. c).

Example 194

Obtain 6-{3-chloro-4-[(3-terbisil)oxy]phenyl}-6,7,8,9-tetrahydro-3,5,6,9a-tetrazoles[cd]azulene

A mixture of N-{3-chloro-4-[(3-terbisil)oxy]phenyl}-5-(3-chloropropyl)-5H-pyrrolo[3,2-d]pyrimidine-4-amine (839 mg), 3-chloro-4-[(3-terbisil)oxy]aniline (1.10 g) and 1-methyl-2-pyrrolidone (5 ml) was stirred at 140°C for 1 h, the Reaction mixture was poured into water (10 ml) and the mixture brought up to pH 8 with a saturated aqueous solution of sodium bicarbonate. The mixture was extracted with ethyl acetate (40 ml×3), the organic layers were combined and dried over anhydrous magnesium sulfate. After concentration under reduced pressure the residue was subjected to chromatography on a column of silica gel (eluent: hexane:ethyl acetate=60:40→50:50) and again subjected to chromatography on a column with a basic silica gel (eluent: hexane:ethyl acetate=80:20→0:100). The target fraction was concentrated under reduced pressure. To the residue was added a mixture of chloroform-diisopropyl ether, the solid was separated by filtration easily. Recrystallization from ethyl acetate gave specified in the header connection (74,5 mg).

1H-NMR (DMSO-d6) δ: 2,31 (2H, m), 3,88 (2H, m), or 4.31 (2H, m), 5,27 (2H, c), 6,47 (1H, d, J=3.0 Hz), 7,14 and 7.36 (5H, m), 7,42 (1H, d, J=2.4 Hz), 7,47 (1H, m), the 7.65 (1H, d, J=3.0 Hz), 8,02 (1H, c).

Example 195

Obtain 6-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-6,7,8,9-tetrahydro-3,5,6,9a-tetrazoles[cd]azulene

(i) Obtaining 5-(3-chloropropyl)-N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine

A mixture of 4-chloro-5-(3-chloropropyl)-5H-pyrrolo[3,2-d]pyrimidine (789 mg), 3-chloro-4-[3-(trifluoromethyl)phenoxy]aniline (1,09 g) and isopropyl alcohol (5 ml) was stirred at 80°C for 4.5 h, the Mixture was concentrated under reduced pressure, was added to the residue saturated aqueous solution of sodium bicarbonate (30 ml) and the mixture was extracted with ethyl acetate (40 ml×3). The organic layers were combined, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (eluent: hexane:ethyl acetate=90:10→20:80) to obtain specified in the connection header (1,46 g).

1H-NMR (CDCl3) δ: 2,39 (2H, m), of 3.60 (2H, t, J=5.6 Hz), a 4.53 (2H, t, J=6.9 Hz), 6,62 (1H, d, J=3.3 Hz), of 6.96 (1H, user. c), 7,07 (1H, d, J=8.7 Hz), 7,08-7,49 (6H, m), 7,87 (1H, m), 8,55 (1H, c).

(ii) Obtain 6-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-6,7,8,9-tetrahydro-3,5,6,9a-tetrazoles[cd]azulene/p>

A mixture of 5-(3-chloropropyl)-N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidine-4-amine (470 mg), potassium carbonate (270 mg) and ethylene glycol (10 ml) was stirred at room temperature for 18.5 hours and at 60°C for 4 h, the Reaction mixture was poured into aqueous sodium hydrogen carbonate solution (20 ml) and the mixture was extracted with ethyl acetate (50 ml×2). The organic layers were combined, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (eluent: hexane:ethyl acetate=90:10→0:100) and the obtained solid substance was recrystallized from a mixture of ethanol-water to obtain specified in the title compound (116 mg).

1H-NMR (DMSO-d6) δ: of 2.45 (2H, m)to 3.99 (2H, t, J=4,8 Hz), 4,34 (2H, t, J=5.4 Hz), of 6.65 (1H, d, J=3.0 Hz), 7,06 (1H, d, J=9.0 Hz), 7,16-7,22 (2H, m), 7,28 (1H, m), 7,33 (1H, d, J=3.0 Hz), 7,37 (1H, m), 7,42 (1H, d, J=2,4 Hz), 7,46 (1H, m), at 8.36 (1H, c).

Example 196

Getting 2-{2-[7-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-1H-pyrazolo[4,3-d]pyrimidine-1-yl}ethoxy}ethanol

(i) Obtaining 2-{2-[7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidine-1-yl]ethoxy}ethylbenzoic

A mixture of 7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidine (747 mg), 2-{2-[(methylsulphonyl)oxy]ethoxy}etilbenzene (1,43 g), potassium carbonate (931 mg) and N,N-dimethylformamide (12 ml) was stirred at 60°C for 4 h, the Reaction mixture was poured into water (30 ml) and see what camping was extracted with ethyl acetate (50 ml×2). The organic layers were combined, washed with saturated salt solution and dried over anhydrous magnesium sulfate. After concentration under reduced pressure the residue was purified by chromatography on a column of silica gel (eluent: hexane:ethyl acetate=80:20→20:80) and was further purified by chromatography on a column with a basic silica gel (eluent: hexane:ethyl acetate=90:10→40:60) to obtain the specified title compound (533 mg).

1H-NMR (CDCl3) δ: to 2.67 (3H, c in), 3.75 (2H, m)to 4.01 (2H, m), to 4.38 (2H, m), to 4.87 (2H, t, J=5.8 Hz), 7,38-of 7.48 (3H, m), to $ 7.91-of 7.95 (2H, m), 8,11 (1H, c), 8,71 (1H, c).

(ii) Obtain 2-{2-[7-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-1H-pyrazolo[4,3-d]pyrimidine-1-yl]ethoxy}ethanol

A mixture of 2-{2-[7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidine-1-yl]ethoxy}etilbenzene (200 mg), 3-chloro-4-[(3-terbisil)oxy]aniline (140 mg), pyridine hydrochloride (96 mg) and 1-methyl-2-pyrrolidone (5 ml) was stirred at 140°C in a period of 16.5 hours, the Reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution (30 ml) and was extracted with ethyl acetate (30 ml×3). The organic layers were combined, washed with saturated salt solution and dried over anhydrous magnesium sulfate. After concentration under reduced pressure the residue was subjected to chromatography on a column of silica gel (eluent: hexane:ethyl acetate=90:10→20:80). The target fraction was concentrated under reduced pressure and the residue was dissolved in methanol(5 ml). Added 1N. an aqueous solution of sodium hydroxide (1 ml) and the mixture was stirred at room temperature for a period of 11.5 hours After concentrating the reaction mixture under reduced pressure was added water (30 ml) and the mixture was extracted with ethyl acetate (45 ml×2). The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (eluent: hexane:ethyl acetate=80:20→0:100) and recrystallized from a mixture of ethanol-ethyl acetate to obtain specified in the title compound (78 mg).

1H-NMR (DMSO-d6) δ: 3,30-3,55 (4H, m), a 3.87 (2H, m), of 4.67 (1H, m), a 4.86 (2H, m), of 5.26 (2H, c), 7,14-to 7.35 (4H, m), 7,46 (1H, m), 7,60 (1H, d, J=8,4 Hz), 7,92 (1H, m), 8,18 (1H, c), 8,35 (1H, c), 8,99 (1H, user. c).

Example 197

Getting 2-{2-[7-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-1H-pyrazolo[4,3-d]pyrimidine-1-yl]ethoxy}ethanol

A mixture of 2-{2-[7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidine-1-yl]ethoxy}etilbenzene (328 mg), 3-chloro-4-[3-(trifluoromethyl)phenoxy]aniline (264 mg), pyridine hydrochloride (159 mg) and 1-methyl-2-pyrrolidone (7.5 ml) was stirred at 140°C for a 33.5 hours, the Reaction mixture was poured into a saturated aqueous solution of sodium bicarbonate (15 ml) and was extracted with ethyl acetate (35 ml×2). The organic layers were combined and dried over anhydrous magnesium sulfate. After concentration under reduced pressure the Sri residue was subjected to chromatography on a column of silica gel (eluent: hexane:ethyl acetate=80:20→0:100). The target fraction was concentrated under reduced pressure and the residue was dissolved in methanol (5 ml). Added 1N. an aqueous solution of sodium hydroxide (1 ml) and the mixture was stirred at room temperature for 2 hours After concentrating the reaction mixture under reduced pressure was added water (30 ml) and the mixture was extracted with ethyl acetate (40 ml×2). The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (eluent: hexane:ethyl acetate=80:20→0:100) and recrystallized from a mixture of ethyl acetate-hexane to obtain specified in the title compound (50 mg).

1H-NMR (DMSO-d6) δ: 3.40 in-3,55 (4H, m), 3,88 (2H, m), and 4.68 (1H, m), 4,89 (2H, m), 7,20-7,24 (2H, m), 7,33 (1H, d, J=8.7 Hz), 7,47 (1H, d, J=7.5 Hz), a 7.62 (1H, m), to 7.77 (1H, m), 8,13 (1H, c), by 8.22 (1H, c), 8,44 (1H, m), 9,23 (1H, user. c).

Example 198

Getting 2-{2-[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-6-methyl-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethoxy}ethanol

(i) Obtaining 4-phenoxy-6-prop-1-in-1-Yeremey-5-amine

4-Iodine-6-phenoxypyridine-5-amine (5,00 g) was dissolved in a mixed solvent of N,N-dimethylformamide (100 ml)triethylamine (50 ml) and successively added 1-(trimethylsilyl)-1-propyne (3,3 ml), TRANS-dichlorobis(triphenylphosphine)palladium(II) (557,7 mg), triphenylphosphine (421,1 mg), copper iodide(I) (303,0 mg) and potassium fluoride (129 g). The mixture was stirred at 60°C in a stream of argon for 16 hours, the Reaction mixture was treated with saturated aqueous sodium bicarbonate and was extracted with diethyl ether. The organic layer was washed with saturated salt solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by chromatography on a column of silica gel (eluent: hexane:ethyl acetate=80:20→50:50) to obtain the specified title compound (2.64 g) as an orange solid.

1H-NMR (CDCl3) δ: 2,19 (3H, c), 4,36 (2H, user. c), 7,07-7,22 (2H, m), 7,22-7,34 (1H, m), 7,35-rate of 7.54 (2H, m), 8,08 (1H, c).

(ii) Obtaining 6-methyl-4-phenoxy-5H-pyrrolo[3,2-d]pyrimidine

4 Phenoxy-6-prop-1-in-1-Yeremey-5-amine (776,0 mg) was dissolved in tetrahydrofuran (30 ml) and cooled to 0°C. To the resulting solution was added dropwise 1.0m solution (4 ml) of tert-butoxide potassium in tetrahydrofuran and the mixture was stirred at room temperature for 30 minutes was Added to the reaction mixture water and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by chromatography on a column of silica gel (eluent: hexane:ethyl acetate=67:33→20:80) to obtain specified in the connection header (578,6 mg) in the form Belogorodka substances.

1H-NMR (CDCl3) δ: 2,54 (3H, c), 6,44 (1H, q, J=1.0 Hz), 7,21-7,30 (3H, m), 7,41-of 7.48 (2H, m), of 8.47 (1H, c), 8,55 (1H, user. c).

(iii) Obtaining 2-[2-(6-methyl-4-phenoxy-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethoxy]ethylbenzoic

6-Methyl-4-phenoxy-5H-pyrrolo[3,2-d]pyrimidine (299,9 mg) and 2-{2-[(methylsulphonyl)oxy]ethoxy}ethylbenzoic (464,1 mg) was dissolved in N,N-dimethylformamide (7 ml), was added potassium carbonate (431 mg) and the mixture was stirred at 60°C for 21 hours was Added to the reaction mixture water and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by chromatography on a column of silica gel (eluent: hexane:ethyl acetate=80:20→20:80) to obtain specified in the connection header (517,8 mg) as a yellow oil.

1H-NMR (CDCl3) δ: 2,50 (3H, c), 3,62-3,74 (2H, m)to 3.92 (2H, t, J=5 Hz), 4,33-of 4.44 (2H, m), of 4.57 (2H, t, J=5 Hz), 6,36 (1H, c), 7,15-7,34 (3H, m), 7,34-7,51 (4H, m), 7,51-the 7.65 (1H, m), 7,87-of 8.00 (2H, m), 8,40 (1H, c).

(iv) Obtain 2-{2-[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-6-methyl-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethoxy}ethylbenzoic

A mixture of 2-[2-(6-methyl-4-phenoxy-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethoxy]ethylbenzoic (92,3 mg), 3-chloro-4-[(3-terbisil)oxy]aniline (86,3 mg), pyridine hydrochloride (81,6 mg) and phenol (156,1 mg) was stirred at 120°C for 3 h at 140°C for 5.5 h and Then was added the hydrochloride of p is Regina (77,6 mg) and phenol (amounts to 188.7 mg) and the mixture was stirred at 140°C in a period of 22.5 hours The reaction mixture was diluted with dichloromethane, washed with saturated salt solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by chromatography on a column with a basic silica gel (eluent: hexane:ethyl acetate=50:50→0:100) to obtain specified in the connection header (33.3 mg) as a purple oil.

1H-NMR (CDCl3) δ: 2,43 (3H, c), 3,88-of 3.97 (2H, m)4,00 (2H, t, J=4.4 Hz), 4,42-4,55 (4H, m), 5,04 (2H, c), 6,38 (1H, c), of 6.71 (1H, d, J=8,8 Hz), 6,93-to 7.09 (1H, m), 7,13-7,42 (6H, m), 7,46-7,58 (1H, m), the 7.65 (1H, d, J=2,6 Hz), 7,74-a 7.85 (2H, m), 8,40 (1H, c), 8,48 (1H, c).

(v) Obtain 2-{2-[4-({3-chloro-4-[(3-terbisil)oxy]phenyl}amino)-6-methyl-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethoxy}ethanol

2-{2-[4-({3-Chloro-4-[(3-terbisil)oxy]phenyl}amino)-6-methyl-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethoxy}ethylbenzoic (90,0 mg) was dissolved in methanol (1 ml), was added 1N. an aqueous solution of sodium hydroxide (0.3 ml) and the mixture was stirred at room temperature for 5 hours, the Reaction mixture was neutralized 1H. hydrochloric acid and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by chromatography on a column with a basic silica gel (eluent: hexane:ethyl acetate=33:67→0:100) to obtain specified in the connection header (43,9 mg) in VI is e pale yellow powder.

1H-NMR (DMSO-d6) δ of 2.45 (3H, c), of 3.46-to 3.52 (4H, m), 3,82 (2H, t, J=4,7 Hz)to 4.52 (2H, t, J=4.3 Hz), with 4.64-4,80 (1H, m), 5,23 (2H, c), 6,30 (1H, c), 7,10-7,24 (2H, m), 7,26-7,38 (2H, m), 7,41-of 7.55 (2H, m), 7,82 (1H, d, J=2,8 Hz), 8,21 (1H, c), 8,68 (1H, c).

Example 199

Getting 2-{2-[4-({3-chloro-4-[3-(triptoreline)phenoxy]phenyl}amino)-6-methyl-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethoxy}ethanol

(i) Obtaining 2-{2-[4-({3-chloro-4-[3-(triptoreline)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethoxy}ethylbenzoic

Specified in the header connection (288,2 mg) was obtained as a pale pink oil interaction, analogous to the methods of example 198 (iv)using 2-[2-(6-methyl-4-phenoxy-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethoxy]ethylbenzoic (271,0 mg), 3-chloro-4-[3-(triptoreline)phenoxy]aniline (297,3 mg), pyridine hydrochloride (235,0 mg) and phenol (497,9 mg).

1H-NMR (CDCl3) δ: of 2.45 (3H, c), 3,92-4,00 (2H, m), Android 4.04 (2H, t, J=4.4 Hz), 4,45-4,55 (4H, m), 6.42 per (1H, c), 6,75-6,85 (3H, m), 6,85-of 6.96 (2H, m), 7,19-7,37 (3H, m), 7,45-7,53 (1H, m), 7,75-of 7.82 (2H, m), a 7.85 (1H, d, J=2,8 Hz), 8,46 (1H, c), 8,73 (1H, user. c).

(ii) Obtain 2-{2-[4-({3-chloro-4-[3-(triptoreline)phenoxy]phenyl}amino)-6-methyl-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethoxy}ethanol

Specified in the header connection (119,1 mg) was obtained as a white powder interaction, analogous to the methods of example 198 (v), using 2-{2-[4-({3-chloro-4-[3-(triptoreline)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethoxy}ative is Tata (281,5 mg), 1H. an aqueous solution of sodium hydroxide (0.6 ml) and methanol (2 ml).

1H-NMR (DMSO-d6) δ 2,47 (3H, c), 3,44 of 3.56 (4H, m), 3,81-to 3.89 (2H, m), 4,56 (2H, t, J=4.5 Hz), 4,71-rate 4.79 (1H, m), 6.35mm (1H, c), 6,88-to 6.95 (2H, m), 7,06-7,14 (1H, m), 7,26 (1H, d, J=9 Hz), to 7.50 (1H, t, J=9 Hz), 7,66 (1H, DD, J=9 Hz, 2.5 Hz), 8,01 (1H, d, J=2.5 Hz), 8,30 (1H, c), 8,99 (1H, user. c).

Example 200

Getting 4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5-[2-(2-hydroxyethoxy)ethyl]-5H-pyrrolo[3,2-d]pyrimidine-6-carbonitrile

(i) Obtaining 4-(3,3-diethoxypropane-1-Jn-1-yl)-6-phenoxypyridine-5-amine

Specified in the title compound (6.20 g) was obtained as a brown oil interaction, analogous to the methods of example 9 (iv)using 4-iodine-6-phenoxypyridine-5-amine (7.0 g), 3,3-diethoxypropane-1 in (3.8 ml), TRANS-dichlorobis(triphenylphosphine)palladium(II) (783,3 mg), copper iodide(I) (255,2 mg) and a mixture of acetonitrile (160 ml)triethylamine (120 ml).

1H-NMR (CDCl3) δ: of 1.29 (6H, t, J=7.2 Hz), 3,62-of 3.77 (2H, m), of 3.77-3,91 (2H, m), 4,48 (2H, user. c)to 5.56 (1H, c), 7,14-7,21 (2H, m), 7,27-7,33 (1H, m), 7,39-to 7.50 (2H, m), 8,11 (1H, c).

(ii) Obtaining 6-(diethoxylate)-4-phenoxy-5H-pyrrolo[3,2-d]pyrimidine

4-(3,3-Diethoxypropane-1-Jn-1-yl)-6-phenoxypyridine-5-amine (2.30 g) was dissolved in 1-methyl-2-pyrrolidone (7.5 ml) and the mixture was cooled to 0°C. To the resulting solution was added a solution of 7.6 ml) of tert-butoxide potassium 1.0m tetrahydrofuran and the mixture was stirred at 0°C for 30 min and at room t is mperature for 1.5 hours To the reaction mixture were added water and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by chromatography on a column of silica gel (eluent: hexane:ethyl acetate=90:10→50:50) to obtain specified in the connection header (1,34 g) as a pale orange solid.

1H-NMR (CDCl3) δ: of 1.29 (6H, t, J=7,1 Hz), 3,52 of 3.75 (4H, m), 5,78 (1H, c), of 6.66 (1H, user. d, J=2.2 Hz), 7,26-7,34 (3H, m), 7,42-7,52 (2H, m), charged 8.52 (1H, c), of 8.95 (1H, user. c).

(iii) Obtaining 4-phenoxy-5H-pyrrolo[3,2-d]pyrimidine-6-carbaldehyde

6-(Diethoxylate)-4-phenoxy-5H-pyrrolo[3,2-d]pyrimidine (3.15 g) was dissolved in tetrahydrofuran (40 ml), was added 1N. hydrochloric acid (40 ml) and the mixture was stirred at room temperature for 2 hours, the Reaction mixture was neutralized 1H. aqueous solution of sodium hydroxide and was extracted with a mixed solvent of ethyl acetate : tetrahydrofuran=1/1. The organic layer was washed with saturated salt solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The precipitate was separated by filtration and dried to obtain specified in the title compound (2.17 g) as a yellow powder.

1H-NMR (DMSO-d6) δ: 7,25-7,40 (3H, m), 7,43-7,58 (3H, m), 8,44 (1H, c), 10,06 (1H, c), 13,26 (1H, c).

(iv) Obtaining phenoxy-5H-pyrrolo[3,2-d]pyrimidine-6-carboxylic acid

4 Phenoxy-5H-pyrrolo[3,2-d]pyrimidine-6-carbaldehyde (2.17 g) was dissolved in dimethyl sulfoxide (21 ml) and the solution was added sodium dihydrophosphate (of 5.45 g) in water (14 ml). To the resulting solution was added dropwise a solution of sodium chlorite (of 2.06 g) in water (14 ml) and the mixture was stirred for 2 hours To the reaction mixture was gradually added a saturated aqueous solution of sodium bicarbonate and the pH of the solution brought up to 2-3 by addition of 1N. hydrochloric acid. The precipitate was separated by filtration, washed with water and diisopropyl ether and dried to obtain specified in the connection header (2,40 g) as a white powder.

1H-NMR (DMSO-d6) δ: to 7.09 (1H, c), 7.23 percent and 7.36 (3H, m), 7,41-rate of 7.54 (2H, m), at 8.36 (1H, c), 12,82 (1H, c).

(v) Obtaining 4-phenoxy-5H-pyrrolo[3,2-d]pyrimidine-6-carboxamide

Thionyl chloride (7 ml) was added to 4-phenoxy-5H-pyrrolo[3,2-d]pyrimidine-6-carboxylic acid (465,0 mg) and the mixture was stirred at 75°C for 2 h, the Reaction mixture was concentrated under reduced pressure and suspended in tetrahydrofuran (10 ml). The resulting suspension was slowly added to aqueous ammonia (20 ml) and the precipitate was separated by filtration. The filtrate was extracted with a mixed solvent of ethyl acetate : tetrahydrofuran=1/1, washed with saturated salt solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The precipitate was separated f is trovanjem, combined with the precipitate collected by filtration before, and was dried to obtain specified in the connection header (427,4 mg) as pale yellow powder.

1H-NMR (DMSO-d6) δ: 7,25 (1H, c), 7,27-to 7.35 (3H, m), 7,39-EUR 7.57 (2H, m), of 7.75 (1H, c), 8,17 (1H, c), at 8.36 (1H, c), to 12.58 (1H, c).

(vi) Obtaining 4-phenoxy-5H-pyrrolo[3,2-d]pyrimidine-6-carbonitrile

4 Phenoxy-5H-pyrrolo[3,2-d]pyrimidine-6-carboxamide (1,67 g) suspended in phosphorus oxychloride (20 ml) and the suspension was stirred at 70°C for 3 hours the Reaction mixture was concentrated under reduced pressure and the residue was dissolved in tetrahydrofuran (25 ml). To the solution was added water and the aqueous ammonia and the mixture was extracted with a mixed solvent of ethyl acetate : tetrahydrofuran=1/1. The organic layer was washed with saturated salt solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by chromatography on a column of silica gel (eluent: hexane:ethyl acetate=90:10→67:33) to obtain the specified title compound (1.07 g) as a pale yellow powder.

1H-NMR (CDCl3) δ: 7,29-7,39 (3H, m), 7,46-of 7.55 (2H, m), to 7.59 (1H, c), of 8.47 (1H, c), 13,76 (1H, c).

(vii) Obtain 2-{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-6-cyano-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethoxy}ethylbenzoic

4 Phenoxy-5H-pyrrolo[3,2-d]pyrimidine-6-carbonitrile (240,4 mg) was dissolved in N,N-dimethylformamide (5 ml) and add recipients is 2-{2-[(methylsulphonyl)oxy]ethoxy}ethylbenzoic (354,1 mg) and potassium carbonate (354,8 mg). Specified in the header connection (266.5 Azerbaijani mg) was obtained as a colourless oil interaction, analogous to the methods of example 198 (iii), using the obtained as described above mixture.

1H-NMR (CDCl3) δ: of 3.73-with 3.79 (2H, m), of 3.96 (2H, t, J=4.9 Hz), 4,37-4,43 (2H, m), a 4.83 (2H, t, J=4.9 Hz), 7,17 (1H, c), 7,18-of 7.23 (2H, m), 7,27-to 7.35(1H, m), of 7.36-7,49 (4H, m), 7,51-7,58 (1H, m), a 7.85-a 7.92 (2H, m), 8,49 (1H c).

(viii) Obtain 2-{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-6-cyano-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethoxy}ethylbenzoic

Specified in the header connection (282,6 mg) was obtained as a yellow oil interaction, analogous to the methods of example 198 (iv)using 2-{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-6-cyano-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethoxy}etilbenzene (261,5 mg), 3-chloro-4-[3-(trifluoromethyl)phenoxy]aniline (264,4 mg), hydrochloride of pyridine (221,6 mg) and phenol (461,6 mg).

1H-NMR (CDCl3) δ: 3,96-4,06 (2H, m), 4,16-4,22 (2H, m), 4,45-of 4.54 (2H, m), 4,68-rate 4.79 (2H, m), to 6.80 (1H, d, J=8,8 Hz), 7,01-to 7.09 (1H, m), 7,14-7,20 (1H, m), 7,24 (1H, c), 7,27-7,53 (6H, m), 7.68 per-7,76 (2H, m), 7,92 (1H, d, J=2.5 Hz), 8,53 (1H, c), of 8.95 (1H, c).

(ix) Obtaining 4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5-[2-(2-hydroxyethoxy)ethyl]-5H-pyrrolo[3,2-d]pyrimidine-6-carbonitrile

Specified in the header connection (143,2 mg) was obtained as a white powder interaction, analogous to the methods of example 198 (v), using 2-{2-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-6-qi is but-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethoxy}etilbenzene (282,6 mg), 1H. an aqueous solution of sodium hydroxide (0.6 ml) and methanol (3 ml).

1H-NMR (CDCl3) δ: 1.77 in (1H, t, J=4.4 Hz), 3,74-3,88 (4H, m), 4,08-4,16 (2H, m), 4,70-4,80 (2H, m), 7,05-to 7.15 (2H, m), 7,16-7,21 (1H, m), 7,25 (1H, c), 7,30 and 7.36 (1H, m), the 7.43 (1H, t, J=7.8 Hz), to 7.67 (1H, DD, J=8,8 Hz, 2,8 Hz), of 7.96 (1H, d, J=2,8 Hz), 8,58 (1H, c), 9,03 (1H, c).

Example 201

Obtain hydrochloride of 2-{3-[4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl]propoxy}ethanol

(i) Obtaining 3-[2-(tetrahydro-2H-Piran-2-yloxy)ethoxy]propylaminosulfonyl

60% sodium Hydride (8,05 g) suspended in N,N-dimethylformamide (80 ml) and the suspension was cooled to 0°C. was Added dropwise a solution of propane-1,3-diol (7.2 ml) in N,N-dimethylformamide (10 ml) and the mixture was stirred at 0°C for 1 h To the reaction solution was added dropwise a solution of 2-(2-bromoethoxy)tetrahydro-2H-Piran (4,0 ml) in N,N-dimethylformamide (10 ml) and the mixture was stirred at 0°C within 2 hours was Added to the reaction mixture, a saturated aqueous solution of ammonium chloride and the mixture was extracted with diethyl ether and ethyl acetate. The organic layer was washed with saturated salt solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in ethyl acetate (100 ml) was added triethylamine (9 ml) and methanesulfonamide (2.3 ml). The mixture was stirred at room temperature for 3 hours to Relax is to the reaction mixture water and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by chromatography on a column of silica gel (eluent: hexane:ethyl acetate=80:20→20:80) to obtain specified in the connection header (of 3.78 g) as a colourless oil.